Insertion of Lippes Loop by Nurse-Midwives and Doctors

Follow-up studies of 7 to 19 months of two groups of 500 women each in Barbados, in one of which a Lippes loop had been inserted by a doctor and in the other by a nurse-midwife, showed a slightly higher incidence of pregnancy and expulsion of the loop in the second group, though the difference was not statistically significant. The insertion of loops by paramedical personnel when this is an economic necessity is thought not to be contraindicated, but adequate training is essential.     

Introgressive hybridisation between domestic pigs (Sus scrofa domesticus) and endemic Corsican wild boars (S. s. meridionalis): effects of human-mediated interventions

Owing to the intensified domestication process with artificial trait selection, introgressive hybridisation between domestic and wild species poses a management problem. Traditional free-range livestock husbandry, as practiced in Corsica and Sardinia, is known to facilitate hybridisation between wild boars and domestic pigs (Sus scrofa). Here, we assessed the genetic distinctness and genome-wide domestic pig ancestry levels of the Corsican wild boar subspecies S. s. meridionalis, with reference to its Sardinian conspecifics, employing a genome-wide single nucleotide polymorphism (SNP) assay and mitochondrial control region (mtCR) haplotypes. We also assessed the reliance of morphological criteria and the melanocortin-1 receptor (MC1R) coat colour gene to identify individuals with domestic introgression. While Corsican wild boars showed closest affinity to Sardinian and Italian wild boars compared to other European populations based on principal component analysis, the observation of previously undescribed mtCR haplotypes and high levels of nuclear divergence (Weir’s θ > 0.14) highlighted the genetic distinctness of Corsican S. s. meridionalis. Across three complementary analyses of mixed ancestry (i.e., STRUCTURE, PCADMIX, and ELAI), proportions of domestic pig ancestry were estimated at 9.5% in Corsican wild boars, which was significantly higher than in wild boars in Sardinia, where free-range pig keeping was banned in 2012. Comparison of morphologically pure- and hybrid-looking Corsican wild boars suggested a weak correlation between morphological criteria and genome-wide domestic pig ancestry. The study highlights the usefulness of molecular markers to assess the direct impacts of management practices on gene flow between domestic and wild species.Subject terms: Conservation genomics, Genetic hybridization, Structural variation     

Actin-binding protein alpha-actinin-1 interacts with the metabotropic glutamate receptor type 5b and modulates the cell surface expression and function of the receptor

Receptors for neurotransmitters require scaffolding proteins for membrane microdomain targeting and for regulating receptor function. Using a yeast two-hybrid screen, alpha-actinin-1, a major F-actin cross-linking protein, was identified as a binding partner for the C-terminal domain of metabotropic glutamate receptor type 5b (mGlu(5b) receptor). Co-expression, co-immunoprecipitation, and pull-down experiments showed a close and specific interaction between mGlu(5b) receptor and alpha-actinin-1 in both transfected HEK-293 cells and rat striatum. The interaction of alpha-actinin-1 with mGlu(5b) receptor modulated the cell surface expression of the receptor. This was dependent on the binding of alpha-actinin-1 to the actin cytoskeleton. In addition, the alpha-actinin-1/mGlu(5b) receptor interaction regulated receptor-mediated activation of the mitogen-activated protein kinase pathway. Together, these findings indicate that there is an alpha-actinin-1-dependent mGlu(5b) receptor association with the actin cytoskeleton modulating receptor cell surface expression and functioning.     

Efficient photochromism from the network of chemical reactions of 7,4'-dihydroxyflavylium in CTAB micelles.

Differently from water, efficient photochromism with a strong colour contrast has been observed for the multistate compound 7,4'-dihydroxyflavylium in the presence of cetyl trimethylammonium bromide (CTAB) micelles. Two states are responsible for the photochromism: trans-chalcone (inside the micelle) in the dark, and flavylium cation, AH(+), (in bulk water) upon irradiation. The kinetics of the system was characterized by flash photolysis and pH jumps. Evidence that the photochemical process leading to AH(+) occurs in the micelle was achieved. The best colour contrast is obtained at pH = 1.5, from a solution practically colourless in the dark, to an intense yellow upon irradiation (quantum yield 0.4). The system is completely reversible with a lifetime of 38 min at room temperature, and exhibits a reasonable stability. A kinetic model capable of fitting the data from thermal entrance of the compound into the micelle, its ejection to bulk water upon irradiation and quantum yields of the photochemical process is proposed.     

Pro12Ala substitution in the peroxisome proliferator-activated receptor-gamma is associated with increased leptin levels in women with type-2 diabetes mellitus

OBJECTIVE: To analyze the relationship between the peroxisome proliferator-activated receptor-gamma (PPARgamma2) Pro12Ala variant and type-2 diabetes mellitus and its correlation with some cytokine determinants of insulin resistance such as tumor necrosis factor (TNF)-alpha and leptin. METHODS: The PPARgamma2 Pro12Ala genetic polymorphism was studied in 167 type-2 diabetic patients and 63 healthy controls. Serum leptin and plasma-soluble TNF-R2 were measured. RESULTS: Women carriers of the Pro12Ala mutation exhibited higher leptin levels than women non-carriers (median 31.4 vs. 17.5 ng/ml; p < 0.005). sTNF-R2 levels did not show differences between the two genotypes. Analysis by the multiple linear regression model of leptin-body mass index controlled by the PPARgamma2 genotype showed that leptin levels were determined by the Pro12Ala mutation in type-2 diabetic women but not in men. CONCLUSIONS: PPARgamma2 seems to be implicated in leptin homeostasis in type-2 diabetic women.     

Dendritic cells exposed to MVA-based HIV-1 vaccine induce highly functional HIV-1-specific CD8(+) T cell responses in HIV-1-infected individuals

Currently, MVA virus vectors carrying HIV-1 genes are being developed as HIV-1/AIDS prophylactic/therapeutic vaccines. Nevertheless, little is known about the impact of these vectors on human dendritic cells (DC) and their capacity to present HIV-1 antigens to human HIV-specific T cells. This study aimed to characterize the interaction of MVA and MVA expressing the HIV-1 genes Env-Gag-Pol-Nef of clade B (referred to as MVA-B) in human monocyte-derived dendritic cells (MDDC) and the subsequent processes of HIV-1 antigen presentation and activation of memory HIV-1-specific T lymphocytes. For these purposes, we performed ex vivo assays with MDDC and autologous lymphocytes from asymptomatic HIV-infected patients. Infection of MDDC with MVA-B or MVA, at the optimal dose of 0.3 PFU/MDDC, induced by itself a moderate degree of maturation of MDDC, involving secretion of cytokines and chemokines (IL1-ra, IL-7, TNF-α, IL-6, IL-12, IL-15, IL-8, MCP-1, MIP-1α, MIP-1β, RANTES, IP-10, MIG, and IFN-α). MDDC infected with MVA or MVA-B and following a period of 48 h or 72 h of maturation were able to migrate toward CCL19 or CCL21 chemokine gradients. MVA-B infection induced apoptosis of the infected cells and the resulting apoptotic bodies were engulfed by the uninfected MDDC, which cross-presented HIV-1 antigens to autologous CD8(+) T lymphocytes. MVA-B-infected MDDC co-cultured with autologous T lymphocytes induced a highly functional HIV-specific CD8(+) T cell response including proliferation, secretion of IFN-γ, IL-2, TNF-α, MIP-1β, MIP-1α, RANTES and IL-6, and strong cytotoxic activity against autologous HIV-1-infected CD4(+) T lymphocytes. These results evidence the adjuvant role of the vector itself (MVA) and support the clinical development of prophylactic and therapeutic anti-HIV vaccines based on MVA-B.     

BRCA1: a novel prognostic factor in resected non-small-cell lung cancer

Background

Although early-stage non-small-cell lung cancer (NSCLC) is considered a potentially curable disease following complete resection, patients have a wide spectrum of survival according to stage (IB, II, IIIA). Within each stage, gene expression profiles can identify patients with a higher risk of recurrence. We hypothesized that altered mRNA expression in nine genes could help to predict disease outcome: excision repair cross-complementing 1 (ERCC1), myeloid zinc finger 1 (MZF1) and Twist1 (which regulate N-cadherin expression), ribonucleotide reductase subunit M1 (RRM1), thioredoxin-1 (TRX1), tyrosyl-DNA phosphodiesterase (Tdp1), nuclear factor of activated T cells (NFAT), BRCA1, and the human homolog of yeast budding uninhibited by benzimidazole (BubR1).

Methodology and Principal Findings

We performed real-time quantitative polymerase chain reaction (RT-QPCR) in frozen lung cancer tissue specimens from 126 chemonaive NSCLC patients who had undergone surgical resection and evaluated the association between gene expression levels and survival. For validation, we used paraffin-embedded specimens from 58 other NSCLC patients. A strong inter-gene correlation was observed between expression levels of all genes except NFAT. A Cox proportional hazards model indicated that along with disease stage, BRCA1 mRNA expression significantly correlated with overall survival (hazard ratio [HR], 1.98 [95% confidence interval (CI), 1.11-6]; P = 0.02). In the independent cohort of 58 patients, BRCA1 mRNA expression also significantly correlated with survival (HR, 2.4 [95%CI, 1.01-5.92]; P = 0.04).

Conclusions

Overexpression of BRCA1 mRNA was strongly associated with poor survival in NSCLC patients, and the validation of this finding in an independent data set further strengthened this association. Since BRCA1 mRNA expression has previously been linked to differential sensitivity to cisplatin and antimicrotubule drugs, BRCA1 mRNA expression may provide additional information for customizing adjuvant antimicrotubule-based chemotherapy, especially in stage IB, where the role of adjuvant chemotherapy has not been clearly demonstrated.     

Barcelona conference on epigenetics and cancer: 50 years of histone acetylation

The Barcelona Conference on Epigenetics and Cancer (BCEC) was held in Barcelona, Spain, on October 1^st and 2^nd, 2014. The meeting was co-organized by the Cancer Epigenetics and Biology Program (PEBC-IDIBELL) and B·Debate, an initiative of Biocat, with the support of "la Caixa" Foundation. The scientific committee was comprised of leading scientists in the field of epigenetics: Dr. Manel Esteller, director of PEBC-IDIBELL, Dr. Alejandro Vaquero and Dr. Esteban Ballestar, from PEBC-IDIBELL, Juan Ausió from the University of Victoria (Canada), and Marcus Buschbeck, from the Institute of Predictive and Personalized Medicine of Cancer (IMPPC), as BCEC series coordinator. This meeting was the second edition of the BCEC series, which was launched by 5 leading Barcelonan institutes to bring together leading investigators in the fields of epigenetics and chromatin research. The topics discussed during the meeting included the current challenges, opportunities, and perspectives surrounding the study of histone modifications (focusing in acetylation), chromatin structure and gene expression, and the involvement of histone acetylation in physiology and diseases, such as cancer or neurological diseases.     

Genetic and Physiological Diversity in the Diatom Nitzschia inconspicua

Nitzschia inconspicua is an ecologically important diatom species, which is believed to have a widespread distribution and to be tolerant to salinity and to organic or nutrient pollution. However, its identification is not straightforward and there is no information on genetic and ecophysiological diversity within the species. We used morphological, molecular (rbcL and LSU D1–D3), ecophysiological and reproductive data to investigate whether N. inconspicua constitutes a single species with a broad ecological tolerance or two or more cryptic species with shared or different ecological preferences. Molecular genetic data for clones from upstream and deltaic sites in the Ebro River basin (Catalonia, Spain) revealed seven N. inconspicua rbcL + LSU genotypes grouped into three major clades. Two of the clades were related to other Nitzschia and Denticula species, making N. inconspicua paraphyletic and suggesting the need for taxonomic revision. Most clones were observed to be automictic, exhibiting paedogamy, and so the biological species concept cannot be used to establish species boundaries. Although there were morphological differences among clones, we found no consistent differences among genotypes belonging to different clades, which are definable only through sequence data. Nevertheless, separating the genotypes could be important for ecological purposes because two different ecophysiological responses were encountered among them.     

Targeting of substance P induces cancer cell death and decreases the steady state of EGFR and Her2

NK1 is a tachykinin receptor highly relevant to tumorigenesis and metastasis development in breast cancer and other carcinomas. Despite the substantial efforts done to develop potent NK1 receptor antagonists, none of these antagonists had shown good antitumor activity in clinical trials. Now, we have tested the effect of inhibition of the neuropeptide Substance P (SP), a NK1 ligand, as a potential therapeutic approach in cancer. We found that the inhibition of SP with antibodies strongly inhibit cell growth and induce apoptosis in breast, colon, and prostate cancer cell lines. These effects were accompained by a decrease in the mitogen-activated kinase singaling pathway. Interestingly, in some cell lines SP abrogation decreased the steady state of Her2 and EGFR, suggesting that SP-mediated signaling is important for the basal activity of these ErbB receptors. In consequence, we observed a blockade of the cell cycle progression and the inhibition of several cell cycle-related proteins including mTOR. SP inhibition also induced cell death in cell lines resistant to Lapatinib and Trastuzumab that have increased levels of active Her2, suggesting that this therapeutic approach could be also effective for those cancers resistant to current anti-ErbB therapies. Thus, we propose a new therapeutic strategy for those cancers that express NK1 receptor and/or other tachykinin receptors, based in the immuno-blockade of the neuropeptide SP.