Statistical aspects in physical mapping application to the genome of O. oeni strain GM

This work addresses issues around physical maps, in particular, for circular genomes. The overlapping relationship between two fragments obtained by applying two different restriction enzymes, separately, is classified as nonoverlapping, partial overlapping, and total overlapping. A double partial overlapping can also appear in a particular situation. Taking into account DNA fragment lengths and under the assumption that the left-hand endpoints of the two restriction fragments are independent random variables, each of which with a uniform distribution along a circular genome, we present expressions for prior probabilities of those events. This information is combined with hybridization data via Bayes' theorem, in order to evaluate corresponding posterior probabilities. Additionally, we explore a sensitivity analysis to quantify the effect of length variation in the results.     

NABC1 (BCAS1): alternative splicing and downregulation in colorectal tumors

We have identified a new splicing variant of the gene "novel amplified in breast cancer 1," NABC1 (HGMW-approved symbol BCAS1). This variant, which we call NABC1_5B, uses a previously unidentified 135-bp exon. Also in this report, we confirm that NABC1 is overexpressed in breast tumors and show that both NABC1 and NABC1_5B are downregulated in colorectal tumors.     

Eugenol disrupts Plasmodium falciparum intracellular development during the erythrocytic cycle and protects against cerebral malaria

BackgroundMalaria is a parasitic disease that compromises the human host. Currently, control of the Plasmodium falciparum burden is centered on artemisinin-based combination therapies. However, decreased sensitivity to artemisinin and derivatives has been reported, therefore it is important to identify new therapeutic strategies.MethodWe used human erythrocytes infected with P. falciparum and experimental cerebral malaria (ECM) animal model to assess the potential antimalarial effect of eugenol, a component of clove bud essential oil.ResultsPlasmodium falciparum cultures treated with increasing concentrations of eugenol reduced parasitemia in a dose-dependent manner, with IC₅₀ of 532.42 ± 29.55 μM. This effect seems to be irreversible and maintained even in the presence of high parasitemia. The prominent effect of eugenol was detected in the evolution from schizont to ring forms, inducing important morphological changes, indicating a disruption in the development of the erythrocytic cycle. Aberrant structural modification was observed by electron microscopy, showing the separation of the two nuclear membrane leaflets as well as other subcellular membranes, such as from the digestive vacuole. Importantly, in vivo studies using ECM revealed a reduction in blood parasitemia and cerebral edema when mice were treated for 6 consecutive days upon infection.ConclusionsThese data suggest a potential effect of eugenol against Plasmodium sp. with an impact on cerebral malaria.General significanceOur results provide a rational basis for the use of eugenol in therapeutic strategies to the treatment of malaria.     

E-cadherin dysfunction in gastric cancer - Cellular consequences, clinical applications and open questions

E-cadherin plays a major role in cell-cell adhesion and inactivating germline mutations in its encoding gene predispose to hereditary diffuse gastric cancer. Evidence indicates that aside from its recognized role in early tumourigenesis, E-cadherin is also pivotal for tumour progression, including invasion and metastization. Herein, we discuss E-cadherin alterations found in a cancer context, associated cellular effects and signalling pathways, and we raise new key questions that will impact in the management of GC patients and families.     

Case report of isochromosome 17q in acute myeloid leukemia with myelodysplasia-related changes after treatment with a hypomethylating agent

Isochromosome 17q is a relatively common karyotypic abnormality in medulloblastoma, gastric, bladder, and breast cancers. In myeloid disorders, it is observed during disease progression and evolution to acute myeloid leukemia in Philadelphia-positive chronic myeloid leukemia. It has been reported in rare cases of myelodysplastic syndrome, with an incidence of 0.4-1.57%. Two new agents have been approved for treatment of myelodysplastic syndrome/chronic myelomonocytic leukemia. These are the hypomethylating agents, 5-azacytidine and decitabine, recommended by consensus guidelines for high-risk myelodysplastic syndrome patients not eligible for hematopoietic stem cell transplantation. We present a case of chronic myelomonocytic leukemia with normal cytogenetics at diagnosis treated with decitabine (with good response); however, the patient evolved to acute myeloid leukemia with i(17q) shortly after suspending treatment. To the best of our knowledge, this is the first report of acute myeloid leukemia with myelodysplasia-related changes with i(17q) after the use of a hypomethylating agent.     

The XNA world: progress towards replication and evolution of synthetic genetic polymers

Life's diversity is built on the wide range of properties and functions that can be encoded in natural biopolymers such as polypeptides and nucleic acids. However, despite their versatility, the range of chemical functionalities is limited, particularly in the case of nucleic acids. Chemical modification of nucleic acids can greatly increase their functional diversity but access to the full phenotypic potential of such polymers requires a system of replication. Here we review progress in the chemical and enzymatic synthesis, replication and evolution of unnatural nucleic acid polymers, which promises to enable the exploration of a vast sequence space not accessible to nature and deliver ligands, catalysts and materials based on this new class of biopolymers.     

A new bicyclic sesquiterpene from the marine sponge associated fungus Emericellopsis minima

A new sesquiterpene (5E)-2-methyl-5-[(1′R*, 5′R*)-2-methylidene-7-oxobicyclo[3.2.1]oct-6-ylidene]-4-oxopentanoic acid (1) was isolated, in addition to the dihydroisocoumarin cis-(3R, 4R)-4-hydroxymellein, ergosterol peroxide and helvolic acid, from the culture of the fungus Emericellopsis minima associated with the marine sponge Hyrtios erecta. The structures of all the compounds were elucidated using spectroscopic data from 1D, 2D NMR and HRESITOFMS. Compounds 1 and cis-(3R, 4R)-4-hydroxymellein were found to show neither antimicrobial nor the in vitro growth inhibitory activities on three human tumor cell lines.     

Persistent activation of omentum influences the pattern of muscular lesion in the mdx diaphragm

The mdx (X chromosome-linked muscular dystrophy) mouse develops a multi-staged disorder characterized by muscle degeneration and reactive fibrosis. Skeletal muscles of mdx mice are not equally susceptible to degeneration. The aim of this study was to verify whether the intense remodeling of the mdx diaphragm could be attributed to influences from the peritoneal microenvironment and omentum, a lymphohematopoietic tissue rich in progenitor cells and trophic factors. At ages corresponding to increased muscular regeneration (12?weeks) and activation of fibrosis (24?weeks), the mdx omentum exhibited (1) morphological and functional characteristics of activation with enlarged milk-spots, an accumulation of CD4⁺, CD8⁺ and CD19⁺B220⁺ B lymphocytes; (2) the formation of clusters positive for proliferating cell nuclear antigen, mainly in B220⁺-rich areas organized in a follicular structure with a germinative center without any challenge by external antigen inducers; (3) clusters with cells positive for fibroblast growth factor-2, numerous Sca-1⁺CD3^-CD19^-Mac-1^- progenitor cells and increased CD4⁺, CD8⁺ and CD3⁺NK1.1⁺ cells in the peritoneal cavity. Omentectomy reduced areas with F4/80⁺ inflammatory infiltrate the activity of matrix metalloproteases 9 and 2, collagen deposition and areas with regenerating myofibers in the diaphragm. Thus, persistent activation of the omentum influences the pattern of inflammation and regeneration of the mdx diaphragm partly via the activation of progenitor cells and the production of growth factors that influence the physiopathology of the muscular tissue remodeling.