Functional imaging of angiogenesis in an orthotopic model of pancreatic cancer

Pancreatic cancer is a major unsolved health problem. The estimated overall 5-year survival rate of only 1-4% is due to aggressiveness of the disease and the lack of effective systemic therapies. Most pancreatic cancer-related deaths are due to the development of metastases, which represents the culmination of a complex interaction between the host organism and neoplastic cells within the primary tumor. Therefore, the study of tumor-host interaction in the context of the whole organism is necessary to evaluate the pathogenesis of tumor growth and metastasis so that effective therapies can be developed. Recent advances in functional imaging combined with animal models that faithfully recreate the biology of human tumors have elevated our ability to examine these complex interactions. In this review, we will use the example of orthotopic mouse models of pancreatic cancer as a tool to survey the challenges and possibilities of functional imaging of angiogenesis, a critical determinant of metastasis.     

A simple approach for non‐invasive transcranial optical vascular imaging (nTOVI)

In vivo imaging of cerebral vasculature is highly vital for clinicians and medical researchers alike. For a number of years non‐invasive optical‐based imaging of brain vascular network by using standard fluorescence probes has been considered as impossible. In the current paper controverting this paradigm, we present a robust non‐invasive optical‐based imaging approach that allows visualize major cerebral vessels at the high temporal and spatial resolution. The developed technique is simple to use, utilizes standard fluorescent dyes, inexpensive micro‐imaging and computation procedures. The ability to clearly visualize middle cerebral artery and other major vessels of brain vascular network, as well as the measurements of dynamics of blood flow are presented. The developed imaging approach has a great potential in neuroimaging and can significantly expand the capabilities of preclinical functional studies of brain and notably contribute for analysis of cerebral blood circulation in disorder models.

An example of 1 × 1.5 cm color‐coded image of brain blood vessels of mouse obtained in vivo by transcranial optical vascular imaging (TOVI) approach through the intact cranium.     

Understanding trends in biological invasions by introduced mammals in southern South America: a review of research and management

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Three‐dimensional multiphoton/optical coherence tomography for diagnostic applications in dermatology

A preliminary clinical trial using state‐of‐the‐art multiphoton tomography (MPT) and optical coherence tomography (OCT) for three‐dimensional (3D) multimodal in vivo imaging of normal skin, nevi, scars and pathologic skin lesions has been conducted. MPT enabled visualization of sub‐cellular details with axial and transverse resolutions of <2 μm and <0.5 μm, respectively, from a volume of 0.35 × 0.35 × 0.2 mm³ at a frame rate of 0.14 Hz (512 × 512 pixels). State‐of‐the‐art OCT, operating at a center wavelength of 1300 nm, was capable of acquiring 3D images depicting the layered architecture of skin with axial and transverse resolutions ～8 μm and ～20 μm, respectively, from a volume of 7 × 3.5 × 1.5 mm³ at a frame rate of 46 Hz (1024 × 1024 pixels). This study demonstrates the clinical diagnostic potential of MPT/OCT for pre‐screening relatively large areas of skin using 3D OCT to identify suspicious regions at microscopic level and subsequently using high resolution MPT to obtain zoomed in, sub‐cellular level information of the respective regions (© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Ethical consideration in invasion ecology: A marine perspective

Biological introductions of species to regions outside their known natural distribution are considered a major threat to native marine biodiversity and a key consideration for ecological management. For most invasive species in marine systems, however, little is known about potential impacts. If we are to increase our knowledge of the processes and mechanisms behind the spread of nonindigenous species or determine economic or ecological impacts, manipulative ecological field experiments are the best way to unambiguously ascribe causal relationships. For studies of invasions, such research may result in species spread and the establishment of new viable populations. Is it ethical then, to take the risk of potentially modifying or endangering other species, populations or ecosystems? Is it possible to mitigate the risks? Or should invasion ecologists work under restrictions that limit their ability to fully assess the impact of invaders? Consideration of the ethics of experimentation is rarely carried out. As a consequence, we propose a decision model that includes possible risk of escape/establishment versus the value of the research to allow researchers and/or managers to critically evaluate what type of experimental approach is appropriate.     

Long non‐coding RNAs in non‐small cell lung cancer as biomarkers and therapeutic targets

Lung cancer‐associated mortality is the most common cause of cancer death worldwide. Non‐coding RNAs (ncRNAs), with no protein‐coding ability, have multiple biological roles. Long non‐coding RNAs (lncRNAs) are a recently characterized class of ncRNAs that are over 200 nucleotides in length. Many lncRNAs have the ability of facilitating or inhibiting the development and progression of tumours, including non‐small cell lung cancer (NSCLC). Because of their fundamental roles in regulating gene expression, along with their involvement in the biological mechanisms underlying tumourigenesis, they are a promising class of tissue‐ and/or blood‐based cancer biomarkers. In this review, we highlight the emerging roles of lncRNAs in NSCLC, and discuss their potential clinical applications as diagnostic and prognostic markers and as therapeutic targets.     

Gene analysis of Vibrio cholerae NAGV14 pilus and its distribution

Adhesive pilus of Vibrio cholerae 034, strain NAGV14, was genetically analyzed. The deduced amino acid (aa) sequence of the major pilin structural gene (VcfA) was 67% homologous to the MshA pilin in the N-terminal region, but no homology was found in the C-terminal region which contained the antigenic epitopes. Upstream and downstream flanking regions examined were highly homologous to mshB and mshC of the MSHA (mannose-sensitive hemagglutinin) gene locus. A short leader sequence and a pair of cysteines near the C-terminus which are the characteristics of type 4a pilus family were found. The major pilin structural gene of NAGV14 was compared to that of a strain V10 producing non-adhesive pili. The deduced aa sequences showed 60% homology, and the distance between two cysteines in the C-terminal region was different. A total of 177 V. cholerae strains were investigated for the presence of a type 4 pilus gene locus by PCR, and 95% were positive. The major pilin gene of NAGV14 was detected in 4 of 93 V. cholerae non-O1, non-0139 strains tested, but none of the V. cholerae O1 and O139 (72 and 12 strains, respectively). Our result suggested that a type 4 pilus gene locus similar to the MSHA gene locus is widely distributed among V. cholerae strains. We proposed naming this type 4 pilus gene locus the VCF (for V. cholerae flexible pili) gene locus.     

Probing the role of sequence in the assembly of three‐dimensional DNA crystals

DNA is a widely used biopolymer for the construction of nanometer‐scale objects due to its programmability and structural predictability. One long‐standing goal of the DNA nanotechnology field has been the construction of three‐dimensional DNA crystals. We previously determined the X‐ray crystal structure of a DNA 13‐mer that forms a continuously hydrogen bonded three‐dimensional lattice through Watson‐Crick and non‐canonical base pairs. Our current study sets out to understand how the sequence of the Watson‐Crick duplex region influences crystallization of this 13‐mer. We screened all possible self‐complementary sequences in the hexameric duplex region and found 21 oligonucleotides that crystallized. Sequence analysis showed that one specific Watson‐Crick pair influenced the crystallization propensity and the speed of crystal self‐assembly. We determined X‐ray crystal structures for 13 of these oligonucleotides and found sequence‐specific structural changes that suggests that this base pair may serve as a structural anchor during crystal assembly. Finally, we explored the crystal self‐assembly and nucleation process. Solution studies indicated that these oligonucleotides do not form base pairs in the absence of cations, but that the addition of divalent cations leads to rapid self‐assembly to higher molecular weight complexes. We further demonstrate that crystals grown from mixtures of two different oligonucleotide sequences contain both oligonucleotides. These results suggest that crystal self‐assembly is nucleated by the formation of the Watson‐Crick duplexes initiated by a simple chemical trigger. This study provides new insight into the role of sequence for the assembly of periodic DNA structures. © 2015 Wiley Periodicals, Inc. Biopolymers 103: 618–626, 2015.     

Long non‐coding RNA SNHG15 promotes CDK14 expression via miR‐486 to accelerate non‐small cell lung cancer cells progression and metastasis

Long non‐coding RNAs (lncRNAs) have been validated to play important role in multiple cancers, including non‐small cell lung cancer (NSCLC). In present study, our team investigate the biologic role of SNHG15 in the NSCLC tumorigenesis. LncRNA SNHG15 was significantly upregulated in NSCLC tissue samples and cells, and its overexpression was associated with poor prognosis of NSCLC patients. In vitro, loss‐of‐functional cellular experiments showed that SNHG15 silencing significantly inhibited the proliferation, promoted the apoptosis, and induced the cycle arrest at G0//G1 phase. In vivo, xenograft assay showed that SNHG15 silencing suppressed tumor growth of NSCLC cells. Besides, SNHG15 silencing decreased CDK14 protein expression both in vivo and vitro. Bioinformatics tools and luciferase reporter assay confirmed that miR‐486 both targeted the 3′‐UTR of SNHG15 and CDK14 and was negatively correlated with their expression levels. In summary, our study conclude that the ectopic overexpression of SNHG15 contribute to the NSCLC tumorigenesis by regulating CDK14 protein via sponging miR‐486, providing a novel insight for NSCLC pathogenesis and potential therapeutic strategy for NSCLC patients.     

Participation of non‐English‐speaking‐background immigrants in work‐related training

This article uses representative data on a sample of Australian workers to examine whether non‐English‐speaking‐background [NESB] immigrants are disadvantaged in terms of access to, and participation in, employment‐related training. Results from the estimation of logit models explaining participation in various types of training indicate that NESB immigrant workers have much lower probabilities of receiving training, even after holding other individual and employment characteristics constant. Further, this differential was generally found to be most pronounced for those immigrants with English‐language difficulties. Decomposition of the training differential, however, suggests that part of the explanation for the lesser incidence of training among NESB immigrants may well lie in employer‐based discrimination.     

Clinical relevance and functional implications for human leucocyte antigen‐g expression in non‐small‐cell lung cancer

HLA‐G has been documented both in establishment of anti‐tumour immune responses and in tumour evasion. To investigate the clinical relevance of HLA‐G in non‐small‐cell lung cancer (NSCLC), expression status and potential significance of HLA‐G in NSCLC were analysed. In this study, HLA‐G expression in 101 NSCLC primary lesions and plasma soluble HLA‐G (sHLA‐G) from 91 patients were analysed with immunohistochemistry and ELISA, respectively. Correlations between HLA‐G status and various clinical parameters including survival time were evaluated. Meanwhile, functional analysis of transfected cell surface HLA‐G expression and plasma sHLA‐G form NSCLC patients on natural killer (NK) cell cytolysis were performed. Data revealed that HLA‐G was expressed in 41.6% (42/101) NSCLC primary lesions, while undetectable in adjacent normal lung tissues. HLA‐G expression in NSCLC lesions was strongly correlated to disease stages (P= 0.002). Plasma sHLA‐G from NSCLC patients was markedly higher than that in normal controls (P= 0.004), which was significantly associated with the disease stages (I versus IV, P= 0.025; II versus IV, P= 0.029). Patient plasma sHLA‐G level (≥median, 32.0 U/ml) had a significantly shorter survival time (P= 0.044); however, no similar significance was observed for the lesion HLA‐G expression. In vitro data showed that both cell surface HLA‐G and patient plasma sHLA‐G could dramatically decrease the NK cell cytolysis. Our findings indicated that both lesion HLA‐G expression and plasma sHLA‐G in NSCLC is related to the disease stage and can exert immunosuppression to the NK cell cytolysis, indicating that HLA‐G could be a potential therapeutic target. Moreover, plasma sHLA‐G in NSCLC patients could be used as a prognosis factor for NSCLC.     

A minimally invasive technique to assess several life‐history characteristics of the endangered great hammerhead shark Sphyrna mokarran

A dorsal‐fin photo‐identification technique paired with a non‐invasive parallel laser photogrammetry technique was used to non‐invasively identify individual Sphyrna mokarran over time. Based on the data collected over a duration of 59 days, 16 different S. mokarran (mean ± s.d . pre‐caudal length: 220·82 ± 13·66 cm; mean ± s.d . cephalofoil width: 71·38 ± 7·94 cm) were identified using dorsal‐fin photo‐identification, with a mean ± s.d . shark re‐sighting frequency of 4·05 ± 3·06 at‐sea days. The results illustrate a high S. mokarran sighting rate and therefore, the utilization of parallel laser photogrammetry and dorsal‐fin photo‐identification may be a plausible multi‐year approach to aid in non‐invasively determining the growth rate and inter‐annual site fidelity of these animals.     

Reorganization of inter‐chromosomal interactions in the 2q37‐deletion syndrome

Chromosomes occupy distinct interphase territories in the three‐dimensional nucleus. However, how these chromosome territories are arranged relative to one another is poorly understood. Here, we investigated the inter‐chromosomal interactions between chromosomes 2q, 12, and 17 in human mesenchymal stem cells (MSCs) and MSC‐derived cell types by DNA‐FISH. We compared our findings in normal karyotypes with a three‐generation family harboring a 2q37‐deletion syndrome, featuring a heterozygous partial deletion of histone deacetylase 4 (HDAC4) on chr2q37. In normal karyotypes, we detected stable, recurring arrangements and interactions between the three chromosomal territories with a tissue‐specific interaction bias at certain loci. These inter‐chromosomal interactions were confirmed by Hi‐C. Interestingly, the disease‐related HDAC4 deletion resulted in displaced inter‐chromosomal arrangements and altered interactions between the deletion‐affected chromosome 2 and chromosome 12 and/or 17 in 2q37‐deletion syndrome patients. Our findings provide evidence for a direct link between a structural chromosomal aberration and altered interphase architecture that results in a nuclear configuration, supporting a possible molecular pathogenesis.