Aerial surveys suggest long‐term stability in the seasonally ice‐free Foxe Basin (Nunavut) polar bear population

Significant information gaps exist regarding the status of polar bears, especially with respect to the impacts of climate change, across large portions of the Arctic. To obtain an updated abundance estimate for the Foxe Basin population, we conducted comprehensive aerial surveys during the 2009 and 2010 ice‐free seasons, when bears are confined to land. We sampled with mark‐recapture distance sampling protocols on inland and coastal transects and surveyed small islands and remnant ice floes. We observed 816 and 1,003 bears in 2009 and 2010, respectively. Although detection functions differed substantially between years, estimates were consistent between analytical methods and years. Averaging four estimates (two from each year) yielded 2,585 (2,096–3,189) bears, which is similar to an estimate from the 1990s. This result, along with robust cub production, suggests a stable and healthy population despite deteriorating sea ice conditions. Collectively, this and other recent on‐land surveys provide a framework for implementing aerial surveys elsewhere. Although aerial surveys do not yield estimates of vital rates or population growth, they enable more rapid and frequent monitoring than mark‐recapture. Integrating them in long‐term monitoring programs will require consideration of ancillary data to infer status and facilitate setting harvest levels.     

Identification of the F1F0 mitochondrial ATPase as a target for modulating skin pigmentation by screening a tagged triazine library in zebrafish

A triazine-based combinatorial library of small molecules was screened in zebrafish to identify compounds that produced interesting phenotypes. One compound (of 1536 screened) induced a dramatic increase in the pigmentation of early stage zebrafish embryos. This compound, PPA, was also found to increase pigmentation in cultured mammalian melanocytes. The cellular target was identified as the mitochondrial F1F0-ATP synthase (ATPase) by affinity chromatography. Oligomycin, a small molecule known to inhibit the mitochondrial ATPase, competed with PPA for its cellular target in melanocytes. In addition, PPA was shown to alter the membrane potential of mitochondria, consistent with inhibition of the mitochondrial ATPase. Thus, PPA has been successfully used as a chemical probe in a forward chemical genetic approach to establish a link between the phenotype and the protein. The results attest to the power of screening small molecule libraries in zebrafish as a means of identifying mammalian targets and suggest the mitochondrial ATPase as a target for modulating pigmentation in both melanocytes and melanoma cells.     

High Incidence of Neonatal Danger Signs and Its Implications for Postnatal Care in Ghana: A Cross-Sectional Study

Background

Reducing neonatal mortality is a major public health priority in sub-Saharan Africa. Numerous studies have examined the determinants of neonatal mortality, but few have explored neonatal danger signs which potentially cause morbidity. This study assessed danger signs observed in neonates at birth, determined the correlations of multiple danger signs and complications between neonates and their mothers, and identified factors associated with neonatal danger signs.

Methods

A cross-sectional study was conducted in three sites across Ghana between July and September in 2013. Using two-stage random sampling, we recruited 1,500 pairs of neonates and their mothers who had given birth within the preceding two years. We collected data on their socio-demographic characteristics, utilization of maternal and neonatal health services, and experiences with neonatal danger signs and maternal complications. We calculated the correlations of multiple danger signs and complications between neonates and their mothers, and performed multiple logistic regression analysis to identify factors associated with neonatal danger signs.

Results

More than 25% of the neonates were born with danger signs. At-birth danger signs in neonates were correlated with maternal delivery complications (r = 0.20, p < 0.001), and neonatal complications within the first six weeks of life (r = 0.19, p < 0.001). However, only 29.1% of neonates with danger signs received postnatal care in the first two days, and 52.4% at two weeks of life. In addition to maternal complications during delivery, maternal age less than 20 years, maternal education level lower than secondary school, and fewer than four antenatal care visits significantly predicted neonatal danger signs.

Conclusions

Over a quarter of neonates are born with danger signs. Maternal factors can be used to predict neonatal health condition at birth. Management of maternal health and close medical attention to high-risk neonates are crucial to reduce neonatal morbidity in Ghana.     

Identification of an intronic splicing enhancer essential for the inclusion of FGFR2 exon IIIc

The ligand specificity of fibroblast growth factor receptor 2 (FGFR2) is determined by the alternative splicing of exons 8 (IIIb) or 9 (IIIc). Exon IIIb is included in epithelial cells, whereas exon IIIc is included in mesenchymal cells. Although a number of cis elements and trans factors have been identified that play a role in exon IIIb inclusion in epithelium, little is known about the activation of exon IIIc in mesenchyme. We report here the identification of a splicing enhancer required for IIIc inclusion. This 24-nucleotide (nt) downstream intronic splicing enhancer (DISE) is located within intron 9 immediately downstream of exon IIIc. DISE was able to activate the inclusion of heterologous exons rat FGFR2 IIIb and human beta-globin exon 2 in cell lines from different tissues and species and also in HeLa cell nuclear extracts in vitro. DISE was capable of replacing the intronic activator sequence 1 (IAS1), a known IIIb splicing enhancer and vice versa. This fact, together with the requirement for DISE to be close to the 5'-splice site and the ability of DISE to promote binding of U1 snRNP, suggested that IAS1 and DISE belong to the same class of cis-acting elements.     

A Proteomic Approach Identifies Isoform-Specific and Nucleotide-Dependent RAS Interactions

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Erratum to: Modeling precision treatment of breast cancer

During the type-setting of the final version of the article [1] some of the additional files were swapped. The correct files are republished in this Erratum.The online version of the original article can be found under doi:10.1186/s13059-015-0658-5.     

Mitochondrial regulation of insect cell apoptosis: Evidence for permeability transition pore-independent cytochrome-c release in the Lepidopteran Sf9 cells

Role of cytochrome-c in insect cell apoptosis is highly controversial, with many earlier reports suggesting lack of involvement of mitochondrial factors in Drosophila while more recent studies have indicated otherwise, thus warranting more in-depth studies of insect cell apoptosis. In the present study, we investigated mitochondrial involvement during actinomycin-D induced apoptosis in Sf9 Lepidopteran cells. Cytochrome-c was released from mitochondria very early during apoptosis, and was preceded quickly by ROS generation and cardiolipin peroxidation. Albeit cytochrome-c release and apoptosis induction were inhibited by bongkrkicacid (BKA) it appears that the release is independent of permeability transition pore (PTP) as it preceded mitochondrial Ca²⁺ buildup and mitochondrial membrane potential (MMP) loss. Further, the release was found to be unaffected by PTP inhibitor cyclosporin-A. Bax inhibitory peptide BiP-P5 could effectively block both cytochrome-c release and apoptosis induction indicating dependence on Bax-channel formation. Inhibition of apoptosis by FSBA, a nucleotide analog that inhibits apoptosome formation through Apaf1 binding, suggested activity of apoptosome similar to mammalian cells. Mitochondria isolated from treated cells activated caspases in the cytosolic fraction of untreated cells while mitochondrial lysates of treated or untreated cells had similar effect. Sequestering cytochrome-c in mitochondrial lysates inhibited DEVDase activity, and addition of purified cytochrome-c and dATP to Sf9 cytosolic fraction induced DEVDase activity, suggesting that cytochrome-c may be exclusively required for Lepidopteran apoptosis. This is the first detailed study demonstrating mitochondrial regulation of Lepidopteran insect cell apoptosis, and reiterates its homology with mammalian cell apoptosis while showing distinctive differences from earlier reports in Drosophila.     

Cytochrome P450 1A1 (CYP1A1) in blood lymphocytes evidence for catalytic activity and mRNA expression.

Studies initiated to characterise the catalytic activity and expression of CYP1A1 in rat blood lymphocytes revealed significant activity of 7-ethoxyresorufin-O-deethylase (EROD) in rat blood lymphocytes. Pretreatment with 3-methylcholanthrene (MC) and beta-naphthoflavone (NF) resulted in significant induction in the activity of lymphocyte EROD suggesting that like the liver enzyme, EROD activity in lymphocytes is inducible and is mediated by the MC inducible isoenzymes of P450. The increase in the activity of EROD was associated with a significant increase in the apparent Vmax and affinity of the substrate towards EROD. That this increase in the activity of EROD could be primarily due to the increase in the expression of CYP1A1 isoenzymes was demonstrated by RT-PCR and western immunoblotting studies indicating an increase in the expression of CYP1A1 in blood lymphocytes after MC pretreatment. Significant inhibition in the EROD activity of MC induced lymphocyte by anti-CYP1A1/1A2 and alpha-naphthoflavone further provided evidence that the CYP1A1/1A2 isoenzymes are involved in the activity of EROD in blood lymphocytes. The data indicating similarities in the regulation of CYP1A1 in blood lymphocytes with the liver isoenzyme suggests that factors which may affect expression of CYP1A1 in liver may also affect expression in blood lymphocytes and that blood lymphocytes could be used as a surrogates for studying hepatic expression of the xenobiotic metabolising enzymes.