Hepatocellular carcinoma: Review of disease and tumor biomarkers.

© The Author(s) 2016.Hepatocellular carcinoma (HCC) is a common malignancy and now the second commonest global cause of cancer death. HCC tumorigenesis is relatively silent and patients experience late symptomatic presentation. As the option for curative treatments is limited to early stage cancers, diagnosis in non-symptomatic individuals is crucial. International guidelines advise regular surveillance of high-risk populations but the current tools lack sufficient sensitivity for early stage tumors on the background of a cirrhotic nodular liver. A number of novel biomarkers have now been suggested in the literature, which may reinforce the current surveillance methods. In addition, recent metabonomic and proteomic discoveries have established specific metabolite expressions in HCC, according to Warburgs phenomenon of altered energy metabolism. With clinical validation, a simple and non-invasive test from the serum or urine may be performed to diagnose HCC, particularly benefiting low resource regions where the burden of HCC is highest

Do maternal perceptions of child eating and feeding help to explain the disconnect between reported and observed feeding practices?: A follow-up study

Research demonstrates a mismatch between reported and observed maternal feeding practices. This mismatch may be explained by maternal cognitions, attitudes, and motivations relating to dyadic parent–child feeding interactions. These complex constructs may not be apparent during observations nor evidenced in self-report questionnaire. Therefore, the aim of this study was to use a qualitative approach to gain a more nuanced and contextualized understanding of (a) maternal perceptions of children's food intake control; (b) how parent–child mealtime interactions influence maternal feeding practices; and (c) ways in which mothers may promote healthy child eating and weight outcomes. Semistructured telephone interviews were conducted with 23 mothers (M = 38.4 ± 3.7 years of age) of preschool-aged children (M = 3.8 ± 0.6 years of age, 19 were normal weight, 14 were girls), who had previously completed child feeding questionnaire and participated in two home-based mealtime observations, 12 months apart. Interviews were recorded, transcribed, and themes extracted to create the database. Four major themes emerged: (a) Maternal confidence in children's ability to regulate food intake is variable; (b) Implementing strategies for nurturing healthy relationships with food beyond the dining table; (c) Fostering positive mealtime interactions is valued above the content of what children eat; and (d) Situation-specific practices and inconsistencies. Findings indicate that maternal feeding practices are shaped by both parent and child influences, and child feeding is mostly guided by controlling the family food environment, rather than by directly pressuring or restricting their child's eating. Results also highlighted the need for research to consider both parent and child influences on child feeding

Selective ablation of pillar and deiters' cells severely affects cochlear postnatal development and hearing in mice.

Mammalian auditory hair cells (HCs) are inserted into a well structured environment of supporting cells (SCs) and acellular matrices. It has been proposed that when HCs are irreversibly damaged by noise or ototoxic drugs, surrounding SCs seal the epithelial surface and likely extend the survival of auditory neurons. Because SCs are more resistant to damage than HCs, the effects of primary SC loss on HC survival and hearing have received little attention. We used the Cre/loxP system in mice to specifically ablate pillar cells (PCs) and Deiters' cells (DCs). In Prox1CreER(T2)+/-;Rosa26(DTA/+) (Prox1DTA) mice, Cre-estrogen receptor (CreER) expression is driven by the endogenous Prox1 promoter and, in presence of tamoxifen, removes a stop codon in the Rosa26(DTA/+) allele and induces diphtheria toxin fragment A (DTA) expression. DTA produces cell-autonomous apoptosis. Prox1DTA mice injected with tamoxifen at postnatal days 0 (P0) and P1 show significant DC and outer PC loss at P2-P4, that reaches ∼70% by 1 month. Outer HC loss follows at P14 and is almost complete at 1 month, while inner HCs remain intact. Neural innervation to the outer HCs is disrupted in Prox1DTA mice and auditory brainstem response thresholds in adults are 40-50 dB higher than in controls. The hearing deficit correlates with loss of cochlear amplification. Remarkably, in Prox1DTA mice, the auditory epithelium preserves the ability to seal the reticular lamina and spiral ganglion neuron counts are normal, a key requirement for cochlear implant success. In addition, our results show that cochlear SC pools should be appropriately replenished during HC regeneration strategies

Photoacoustic Reconstruction Using Sparsity in Curvelet Frame: Image Versus Data Domain

Curvelet frame is of special significance for photoacoustic tomography (PAT) due to its sparsifying and microlocalisation properties. We derive a one-to-one map between wavefront directions in image and data spaces in PAT which suggests near equivalence between the recovery of the initial pressure and PAT data from compressed/subsampled measurements when assuming sparsity in Curvelet frame. As the latter is computationally more tractable, investigation to which extent this equivalence holds conducted in this paper is of immediate practical significance. To this end we formulate and compare DR , a two step approach based on the recovery of the complete volume of the photoacoustic data from the subsampled data followed by the acoustic inversion, and p0R , a one step approach where the photoacoustic image (the initial pressure, p0 ) is directly recovered from the subsampled data. Effective representation of the photoacoustic data requires basis defined on the range of the photoacoustic forward operator. To this end we propose a novel wedge-restriction of Curvelet transform which enables us to construct such basis. Both recovery problems are formulated in a variational framework. As the Curvelet frame is heavily overdetermined, we use reweighted ℓ1 norm penalties to enhance the sparsity of the solution. The data reconstruction problem DR is a standard compressed sensing recovery problem, which we solve using an ADMM-type algorithm, SALSA. Subsequently, the initial pressure is recovered using time reversal as implemented in the k-Wave Toolbox. The p0 reconstruction problem, p0R , aims to recover the photoacoustic image directly via FISTA, or ADMM when in addition including a non-negativity constraint. We compare and discuss the relative merits of the two approaches and illustrate them on 2D simulated and 3D real data in a fair and rigorous manner

The priB Gene of Klebsiella pneumoniae Encodes a 104-Amino Acid Protein That Is Similar in Structure and Function to Escherichia coli PriB

Primosome protein PriB is a single-stranded DNA-binding protein that serves as an accessory factor for PriA helicase-catalyzed origin-independent reinitiation of DNA replication in bacteria. A recent report describes the identification of a novel PriB protein in Klebsiella pneumoniae that is significantly shorter than most sequenced PriB homologs. The K. pneumoniae PriB protein is proposed to comprise 55 amino acid residues, in contrast to E. coli PriB which comprises 104 amino acid residues and has a length that is typical of most sequenced PriB homologs. Here, we report results of a sequence analysis that suggests that the priB gene of K. pneumoniae encodes a 104-amino acid PriB protein, akin to its E. coli counterpart. Furthermore, we have cloned the K. pneumoniae priB gene and purified the 104-amino acid K. pneumoniae PriB protein. Gel filtration experiments reveal that the K. pneumoniae PriB protein is a dimer, and equilibrium DNA binding experiments demonstrate that K. pneumoniae PriB's single-stranded DNA-binding activity is similar to that of E. coli PriB. These results indicate that the PriB homolog of K. pneumoniae is similar in structure and in function to that of E. coli

Gene × Gene interaction between MnSOD and GPX-1 and breast cancer risk: a nested case-control study

BACKGROUND: Germ-line mutations in genes such as BRCA1, BRCA2, and ATM can cause a substantial increase in risk of breast cancer. However, these mutations are rare in the general population, and account for little of the incidence of sporadic breast cancer in the general population. Therefore, research has been focused on examining associations between common polymorphisms and breast cancer risk. To date, few associations have been described. This has led to the hypothesis that breast cancer is a complex disease, whereby a constellation of very low penetrance alleles need to be carried to present a risk phenotype. Polymorphisms in the manganese superoxide dismutase (MnSOD) and glutathione peroxidase (GPX-1) genes have been proposed as low penetrance alleles, and have not been clearly associated with breast cancer. We investigated whether variants at both polymorphisms, while not independently associated with breast cancer risk, could influence breast cancer risk when considered together. METHODS: A case-control study nested within the Nurses' Health Study was performed comparing 1262 women diagnosed with breast cancer to 1533 disease free women. The MnSOD (Val16Ala, rs1799725) and GPX-1 (Pro198Leu, rs1050450) were genotyped via TaqMan assay. Disease risk was evaluated using logistic regression. RESULTS: While neither allele alone shows any change in breast cancer risk, an increase in the risk of breast cancer (OR 1.87, 95% CI 1.09 – 3.19) is observed in individuals who carry both the Ala16Ala genotype of MnSOD and the Leu198Leu genotype of GPX-1. CONCLUSION: Polymorphisms in the GPX-1 and MnSOD genes are associated with an increased risk of breast cancer

Inferring human population sizes, divergence times and rates of gene flow from mitochondrial, X and Y chromosome resequencing data

We estimate parameters of a general isolation-with-migration model using resequence data from mitochondrial DNA (mtDNA), the Y chromosome, and two loci on the X chromosome in samples of 25-50 individuals from each of 10 human populations. Application of a coalescent-based Markov chain Monte Carlo technique allows simultaneous inference of divergence times, rates of gene flow, as well as changes in effective population size. Results from comparisons between sub-Saharan African and Eurasian populations estimate that 1500 individuals founded the ancestral Eurasian population similar to 40 thousand years ago (KYA). Furthermore, these small Eurasian founding populations appear to have grown much more dramatically than either African or Oceanian populations. Analyses of sub-Saharan African populations provide little evidence for a history, of population bottlenecks and suggest that die), began diverging from one another upward of 50 KYA. We surmise that ancestral African populations had already been geographically structured prior to the founding of ancestral Eurasian populations. African populations are shown to experience low levels of mitochondrial DNA gene flow, but high levels of Y chromosome gene flow. In particular, Y chromosome gene flow appears to be asymmetric, i.e., from the Bantu-speaking population into other African populations. Conversely, mitochondrial gene flow is more extensive between non-African populations, but appears to be absent between European and Asian Populations

Acoustic Wave Field Reconstruction From Compressed Measurements With Application in Photoacoustic Tomography

We present a method for the recovery of compressively sensed acoustic fields using patterned, instead of point-by-point, detection. From a limited number of such compressed measurements, we propose to reconstruct the field on the sensor plane in each time step independently assuming its sparsity in a Curvelet frame. A modification of the Curvelet frame is proposed to account for the smoothing effects of data acquisition and motivated by a frequency domain model for photoacoustic tomography. An ADMM type algorithm, split augmented Lagrangian shrinkage algorithm, is used to recover the pointwise data in each individual time step from the patterned measurements. For photoacoustic applications, the photoacoustic image of the initial pressure is reconstructed using time reversal in k-Wave Toolbox

Phylogenetic determinants of toxin gene distribution in genomes of Brevibacillus laterosporus

Brevibacillus laterosporus is a globally ubiquitous, spore forming bacterium, strains of which have shown toxic activity against invertebrates and microbes and several have been patented due to their commercial potential. Relatively little is known about this bacterium. Here, we examined the genomes of six published and five newly determined genomes of B. laterosporus, with an emphasis on the relationships between known and putative toxin encoding genes, as well as the phylogenetic relationships between strains. Phylogenetically, strain relationships are similar using average nucleotide identity (ANI) values and multi-gene approaches, although PacBio sequencing revealed multiple copies of the 16S rDNA gene which lessened utility at the strain level. Based on ANI values, the New Zealand isolates were distant from other isolates and may represent a new species. While all of the genomes examined shared some putative toxicity or virulence related proteins, many specific genes were only present in a subset of strains