Differential Protein Expression in Small Intestinal Neuroendocrine Tumors and Liver Metastases

OBJECTIVE: Small intestinal neuroendocrine tumors (SI-NETs) are often detected after they have become metastatic. Using a novel protein array, we identified pathways important in SI-NET metastasis development in surgically resected patients. METHODS: Paired primary tumors and liver metastases from 25 patients undergoing surgical resection for metastatic SI-NETs were harvested. Extracted proteins were separated by sodium dodecyl sulfate gel and multiplex immunoblots were performed with 136 antibodies. Significant Analysis of Microarray was used to select for differentially expressed proteins. A tissue microarray was constructed from 27 archived specimens and stained by immunohistochemistry. RESULTS: Comparing primary SI-NETs with matched normal small-bowel mucosa, 9 proteins were upregulated and cyclin E was downregulated. The SI-NET liver metastases demonstrated upregulation of P-ERK and p27 but downregulation of CDK2 and CDC25B. When comparing primary SI-NET with their paired liver metastases, cyclin E demonstrated a significant upregulation in the liver metastasis. Tissue microarray demonstrated higher p38 expression and lower Cdc 25b expression in SI-NETs versus liver metastases and confirmed higher expression of p27 in liver metastases versus normal liver. CONCLUSIONS: Few studies have compared protein expression in paired primary and metastatic SI-NETs. Our findings reveal changes in a limited number of proteins, suggesting that these may be targets for therapy

Distinct but overlapping roles of LRRTM1 and LRRTM2 in developing and mature hippocampal circuits

LRRTMs are postsynaptic cell adhesion proteins that have region-restricted expression in the brain. To determine their role in the molecular organization of synapses in vivo, we studied synapse development and plasticity in hippocampal neuronal circuits in mice lacking both Lrrtm1 and Lrrtm2. We found that LRRTM1 and LRRTM2 regulate the density and morphological integrity of excitatory synapses on CA1 pyramidal neurons in the developing brain but are not essential for these roles in the mature circuit. Further, they are required for long-term-potentiation in the CA3-CA1 pathway and the dentate gyrus, and for enduring fear memory in both the developing and mature brain. Our data show that LRRTM1 and LRRTM2 regulate synapse development and function in a cell-type and developmental-stage-specific manner, and thereby contribute to the fine-tuning of hippocampal circuit connectivity and plasticity

Thermogravimetric and kinetic analysis of energy crop Jerusalem artichoke using the distributed activation energy model

Jerusalem artichoke has great potential as future feedstock for bioenergy production because of its high tuber yield (up to 90 t ha(-1)), appropriate biomass characteristics, low input demand, and positive environmental impact. The pyrolytic and kinetic characteristics of Jerusalem artichoke tubers were analyzed at heating rates of 5, 10, 20 and 30 A degrees C min(-1). TG and DTG curves in an inert (nitrogen) atmosphere suggested that there were three distinct stages of mass loss and the major loss occurs between about 190-380 A degrees C. Heating rate brought a lateral shift toward right in the temperature. And, it not only affects the temperature at which the highest mass loss rate reached, but also affect the maximum rate of mass loss. The distributed activation energy model (DAEM) was used to study the pyrolysis kinetics and provided reasonable fits to the experimental data. The activation energy (E) of tubers ranged from 146.40 to 232.45 kJ mol(-1), and the frequency factor (A) changed greatly corresponding to E values at different mass conversion.Jerusalem artichoke has great potential as future feedstock for bioenergy production because of its high tuber yield (up to 90 t ha(-1)), appropriate biomass characteristics, low input demand, and positive environmental impact. The pyrolytic and kinetic characteristics of Jerusalem artichoke tubers were analyzed at heating rates of 5, 10, 20 and 30 A degrees C min(-1). TG and DTG curves in an inert (nitrogen) atmosphere suggested that there were three distinct stages of mass loss and the major loss occurs between about 190-380 A degrees C. Heating rate brought a lateral shift toward right in the temperature. And, it not only affects the temperature at which the highest mass loss rate reached, but also affect the maximum rate of mass loss. The distributed activation energy model (DAEM) was used to study the pyrolysis kinetics and provided reasonable fits to the experimental data. The activation energy (E) of tubers ranged from 146.40 to 232.45 kJ mol(-1), and the frequency factor (A) changed greatly corresponding to E values at different mass conversion

Mus musculus deficient for secretory antibodies show delayed growth with an altered urinary metabolome

© 2019 The Author(s). Background: The polymeric immunoglobulin receptor (pIgR) maintains the integrity of epithelial barriers by transporting polymeric antibodies and antigens through the epithelial mucosa into the lumen. In this study, we examined the role of pIgR in maintaining gut barrier integrity, which is important for the normal development in mice. Methods: Cohorts of pIgR -/- mice and their wildtype controls were housed under Specific Pathogen Free (SPF) conditions and monitored for weight gain as an indicator of development over time. The general physiology of the gastrointestinal tract was analysed using immunohistochemistry in young (8-12 weeks of age) and aged mice (up to 18 months of age), and the observed immunopathology in pIgR -/- mice was further characterised using flow cytometry. Urinary metabolites were analysed using gas chromatography-mass spectrometry (GC-MS), which revealed changes in metabolites that correlated with age-related increase in gut permeability in pIgR -/- mice. Results: We observed that pIgR -/- mice exhibited delayed growth, and this phenomenon is associated with low-grade gut inflammation that increased with ageing. The gross intraepithelial lymphocytic (IEL) infiltration characteristic of pIgR -/- mice was redefined as CD8α+αβ+ T cells, the majority of which expressed high levels of CD103 and CD69 consistent with tissue resident memory T cells (TRM). Comparison of the urinary metabolome between pIgR -/- and wild-type mice revealed key changes in urinary biomarkers fucose, glycine and Vitamin B5, suggestive of altered mucosal permeability. A significant increase in gut permeability was confirmed by analysing the site-specific uptake of sugar probes in different parts of the intestine. Conclusion: Our data show that loss of the secretory antibody system in mice results in enhanced accumulation of inflammatory IELs in the gut, which likely reflects ongoing inflammation in reaction to gut microbiota or food antigens, leading to delayed growth in pIgR -/- mice. We demonstrate that this leads to the presence of a unique urinary metabolome profile, which may provide a biomarker for altered gut permeability

Chromosomal rearrangements and karyotype evolution in carnivores revealed by chromosome painting

Chromosomal evolution in carnivores has been revisited extensively using cross-species chromosome painting. Painting probes derived from flow-sorted chromosomes of the domestic dog, which has one of the most rearranged karyotypes in mammals and the highest dipoid number (2n=78) in carnivores, are a powerful tool in detecting both evolutionary intra- and inter-chromosomal rearrangements. However, only a few comparative maps have been established between dog and other non-Canidae species. Here, we extended cross-species painting with dog probes to seven more species representing six carnivore families: Eurasian lynx (Lynx lynx), the stone marten (Martes foina), the small Indian civet (Viverricula indica), the Asian palm civet (Paradoxurus hermaphrodites), Javan mongoose (Hepestes javanicas), the raccoon (Procyon lotor) and the giant panda (Ailuropoda melanoleuca). The numbers and positions of intra-chromosomal rearrangements were found to differ among these carnivore species. A comparative map between human and stone marten, and a map among the Yangtze finless porpoise (Neophocaena phocaenoides asiaeorientalis), stone marten and human were also established to facilitate outgroup comparison and to integrate comparative maps between stone marten and other carnivores with such maps between human and other species. These comparative maps give further insight into genome evolution and karyotype phylogenetic relationships among carnivores, and will facilitate the transfer of gene mapping data from human, domestic dog and cat to other species

Pyrolytic and Kinetic Analysis of Two Coastal Plant Species: Artemisia annua and Chenopodium glaucum

The large amount of coastal plant species available makes them ideal candidates for energy production. In this study, thermogravimetric analysis was used to evaluate the fuel properties of two coastal plant species, and the distributed activation energy model (DAEM) was employed in kinetic analysis. The major mass loss due to devolatilization started at 154 and 162 degrees C at the heating rate of 10 degrees C min(-1) for Artemisia annua and Chenopodium glaucum, respectively. The results showed that the average activation energies of Artemisia annua and Chenopodium glaucum were 169.69 and 170.48 kJ mol(-1), respectively. Furthermore, the activation energy changed while the conversion rate increased, and the frequency factor k(0) decreased greatly while the activation energy decreased. The results also indicated that the devolatilization of the two coastal plant species underwent a set of first-order reactions and could be expressed by the DAEM. Additionally, a simplified mathematical model was proposed to facilitate the prediction of devolatilization curves.The large amount of coastal plant species available makes them ideal candidates for energy production. In this study, thermogravimetric analysis was used to evaluate the fuel properties of two coastal plant species, and the distributed activation energy model (DAEM) was employed in kinetic analysis. The major mass loss due to devolatilization started at 154 and 162 degrees C at the heating rate of 10 degrees C min(-1) for Artemisia annua and Chenopodium glaucum, respectively. The results showed that the average activation energies of Artemisia annua and Chenopodium glaucum were 169.69 and 170.48 kJ mol(-1), respectively. Furthermore, the activation energy changed while the conversion rate increased, and the frequency factor k(0) decreased greatly while the activation energy decreased. The results also indicated that the devolatilization of the two coastal plant species underwent a set of first-order reactions and could be expressed by the DAEM. Additionally, a simplified mathematical model was proposed to facilitate the prediction of devolatilization curves

Impact of the Kuroshio intrusion on the nutrient inventory in the upper northern South China Sea: insights from an isopycnal mixing model

Based on four cruises covering a seasonal cycle in 2009-2011, we examined the impact of the Kuroshio intrusion, featured by extremely oligotrophic waters, on the nutrient inventory in the central northern South China Sea (NSCS). The nutrient inventory in the upper 100m of the water column in the study area ranged from similar to 200 to similar to 290 mmol m(-2) for N+N (nitrate plus nitrite), from similar to 13 to similar to 24 mmol m(-2) for soluble reactive phosphate and from similar to 210 to similar to 430 mmol m(-2) for silicic acid. The nutrient inventory showed a clear seasonal pattern with the highest value appearing in summer, while the N+N inventory in spring and winter had a reduction of similar to 13 and similar to 30 %, respectively, relative to that in summer. To quantify the extent of the Kuroshio intrusion, an isopycnal mixing model was adopted to derive the proportional contribution of water masses from the SCS proper and the Kuroshio along individual isopycnal surfaces. The derived mixing ratio along the isopycnal plane was then employed to predict the genuine gradients of nutrients under the assumption of no biogeochemical alteration. These predicted nutrient concentrations, denoted as N-m, are solely determined by water mass mixing. Results showed that the nutrient inventory in the upper 100m of the NSCS was overall negatively correlated to the Kuroshio water fraction, suggesting that the Kuroshio intrusion significantly influenced the nutrient distribution in the SCS and its seasonal variation. The difference between the observed nutrient concentrations and their corresponding Nm allowed us to further quantify the nutrient removal/addition associated with the biogeochemical processes on top of the water mass mixing. We revealed that the nutrients in the upper 100m of the water column had a net consumption in both winter and spring but a net addition in fall.Based on four cruises covering a seasonal cycle in 2009-2011, we examined the impact of the Kuroshio intrusion, featured by extremely oligotrophic waters, on the nutrient inventory in the central northern South China Sea (NSCS). The nutrient inventory in the upper 100m of the water column in the study area ranged from similar to 200 to similar to 290 mmol m(-2) for N+N (nitrate plus nitrite), from similar to 13 to similar to 24 mmol m(-2) for soluble reactive phosphate and from similar to 210 to similar to 430 mmol m(-2) for silicic acid. The nutrient inventory showed a clear seasonal pattern with the highest value appearing in summer, while the N+N inventory in spring and winter had a reduction of similar to 13 and similar to 30 %, respectively, relative to that in summer. To quantify the extent of the Kuroshio intrusion, an isopycnal mixing model was adopted to derive the proportional contribution of water masses from the SCS proper and the Kuroshio along individual isopycnal surfaces. The derived mixing ratio along the isopycnal plane was then employed to predict the genuine gradients of nutrients under the assumption of no biogeochemical alteration. These predicted nutrient concentrations, denoted as N-m, are solely determined by water mass mixing. Results showed that the nutrient inventory in the upper 100m of the NSCS was overall negatively correlated to the Kuroshio water fraction, suggesting that the Kuroshio intrusion significantly influenced the nutrient distribution in the SCS and its seasonal variation. The difference between the observed nutrient concentrations and their corresponding Nm allowed us to further quantify the nutrient removal/addition associated with the biogeochemical processes on top of the water mass mixing. We revealed that the nutrients in the upper 100m of the water column had a net consumption in both winter and spring but a net addition in fall

Gene cloning and expression profile of a novel carotenoid hydroxylase (CYP97C) from the green alga Haematococcus pluvialis

A full-length complementary DNA (cDNA) sequence of epsilon-ring CHY (designated Haecyp97c) was cloned from the green alga Haematococcus pluvialis by reverse transcription polymerase chain reaction (RT-PCR) and rapid amplification of cDNA ends methods. The Haecyp97c cDNA sequence was 1,995 base pairs (bp) in length, which contained a 1,620-bp open reading frame, a 46-bp 5'-untranslated region (UTR), and a 329-bp 3'-UTR with the characteristic of the poly (A) tail. The deduced protein had a calculated molecular mass of 58.71 kDa with an estimated isoelectric point of 7.94. Multiple alignment analysis revealed that the deduced amino acid sequence of HaeCYP97C shared high identity of 72-85 % with corresponding CYP97Cs from other eukaryotes. The catalytic motifs of cytochrome P450s were detected in the amino acid sequence of HaeCYP97C. The transcriptional levels of Haecyp97c and xanthophylls accumulation under high light (HL) stress have been examined. The results revealed that Haecyp97c transcript was strongly increased after 13-28 h under HL stress. Meanwhile, the concentrations of chlorophylls, carotenes, and lutein were decreased, and zeaxanthin and astaxanthin concentrations were increased rapidly, respectively. These facts indicated that HaeCYP97C was perhaps involved in xanthophyll biosynthesis, which plays an important role in adaption to HL for H. pluvialis.A full-length complementary DNA (cDNA) sequence of epsilon-ring CHY (designated Haecyp97c) was cloned from the green alga Haematococcus pluvialis by reverse transcription polymerase chain reaction (RT-PCR) and rapid amplification of cDNA ends methods. The Haecyp97c cDNA sequence was 1,995 base pairs (bp) in length, which contained a 1,620-bp open reading frame, a 46-bp 5'-untranslated region (UTR), and a 329-bp 3'-UTR with the characteristic of the poly (A) tail. The deduced protein had a calculated molecular mass of 58.71 kDa with an estimated isoelectric point of 7.94. Multiple alignment analysis revealed that the deduced amino acid sequence of HaeCYP97C shared high identity of 72-85 % with corresponding CYP97Cs from other eukaryotes. The catalytic motifs of cytochrome P450s were detected in the amino acid sequence of HaeCYP97C. The transcriptional levels of Haecyp97c and xanthophylls accumulation under high light (HL) stress have been examined. The results revealed that Haecyp97c transcript was strongly increased after 13-28 h under HL stress. Meanwhile, the concentrations of chlorophylls, carotenes, and lutein were decreased, and zeaxanthin and astaxanthin concentrations were increased rapidly, respectively. These facts indicated that HaeCYP97C was perhaps involved in xanthophyll biosynthesis, which plays an important role in adaption to HL for H. pluvialis

Study of the surface structure of butterfly wings using the scanning electron microscopic moire method

Scanning electron microscopic (SEM) moire method was used to study the surface structure of three kinds of butterfly wings: Papilio maackii Menetries, Euploea midamus (Linnaeus), and Stichophthalma how-qua (Westwood). Gratings composed of curves with different orientations were found on scales. The planar characteristics of gratings and some other planar features of the surface structure of these wings were revealed, respectively, in terms of virtual strain. Experimental results demonstrate that SEM moire method is a simple, nonlocal, economical, effective technique for determining which grating exists on one whole scale, measuring the dimension and the whole planar structural character of the grating on each scale, as well as characterizing the relationship between gratings on different scales of each butterfly wing. Thus, the SEM moire method is a useful tool to assist with characterizing the structure of butterfly wings and explaining their excellent properties. (c) 2007 Optical Society of America