The Silencing of N-myc Downstream-Regulated Gene-1 in an Orthotopic Pancreatic Cancer Model Leads to More Aggressive Tumor Growth and Metastases

BACKGROUND: The understanding of molecular mechanisms leading to poor prognosis in pancreatic cancer may help develop treatment options. N-myc downstream-regulated gene-1 (NDRG1) has been correlated to better prognosis in pancreatic cancer. Therefore, we thought to analyze how the loss of NDRG1 affects progression in an orthotopic xenograft animal model of recurrence. METHODS: Capan-1 cells were silenced for NDRG1 (C(sil)) or transfected with scrambled shRNA (C(scr)) and compared for anchorage-dependent and anchorage-independent growth, invasion and tube formation in vitro. In an orthotopic xenograft model of recurrence tumors were grown in the pancreatic tail. The effect of NDRG1 silencing was evaluated on tumor size and metastasis. RESULTS: The silencing of NDRG1 in Capan-1 cells leads to more aggressive tumor growth and metastasis. We found faster cell growth, double count of invaded cells and 1.8-fold increase in tube formation in vitro. In vivo local tumors were 5.9-fold larger (p = 0.006) and the number of metastases was higher in animals with tumors silenced for NDRG1 primarily (3 vs. 1.1; p = 0.005) and at recurrence (3.3 vs. 0.9; p = 0.015). CONCLUSION: NDRG1 may be an interesting therapeutic target as its silencing in human pancreatic cancer cells leads to a phenotype with more aggressive tumor growth and metastasis.

Within-plant distribution of 1,4-benzoxazin-3-ones contributes to herbivore niche differentiation in maize

Plant defences vary in space and time, which may translate into specific herbivore-foraging patterns and feeding niche differentiation. To date, little is known about the effect of secondary metabolite patterning on within-plant herbivore foraging. We investigated how variation in the major maize secondary metabolites, 1,4-benzoxazin-3-one derivatives (BXDs), affects the foraging behaviour of two leaf-chewing herbivores. BXD levels varied substantially within plants. Older leaves had higher levels of constitutive BXDs while younger leaves were consistently more inducible. These differences were observed independently of plant age, even though the concentrations of most BXDs declined markedly in older plants. Larvae of the well-adapted maize pest Spodoptera frugiperda preferred and grew better on young inducible leaves irrespective of plant age, while larvae of the generalist Spodoptera littoralis preferred and tended to grow better on old leaves. In BXD-free mutants, the differences in herbivore weight gain between old and young leaves were absent for both species, and leaf preferences of S. frugiperda were attenuated. In contrast, S. littoralis foraging patterns were not affected. In summary, our study shows that plant secondary metabolites differentially affect performance and foraging of adapted and non-adapted herbivores and thereby likely contribute to feeding niche differentiation

Kawasaki syndrome: Cluster analysis of incident cases presenting to a pediatric tertiary care hospital in Texas from January 1, 2005 to December 31, 2009

Background: Despite almost 40 years of research into the etiology of Kawasaki Syndrome (KS), there is little research published on spatial and temporal clustering of KS cases. Previous analysis has found significant spatial and temporal clustering of cases, therefore cluster analyses were performed to substantiate these findings and provide insight into incident KS cases discharged from a pediatric tertiary care hospital. Identifying clusters from a single institution would allow for prospective analysis of risk factors and potential exposures for further insight into KS etiology. ^ Methods: A retrospective study was carried out to examine the epidemiology and distribution of patients presenting to Texas Children’s Hospital in Houston, Texas, with a diagnosis of Acute Febrile Mucocutaneous Lymph Node Syndrome (MCLS) upon discharge from January 1, 2005 to December 31, 2009. Spatial, temporal, and space-time cluster analyses were performed using the Bernoulli model with case and control event data. ^ Results: 397 of 102,761 total patients admitted to Texas Children’s Hospital had a principal or secondary diagnosis of Acute Febrile MCLS upon over the 5 year period. Demographic data for KS cases remained consistent with known disease epidemiology. Spatial, temporal, and space-time analyses of clustering using the Bernoulli model demonstrated no statistically significant clusters. ^ Discussion: Despite previous findings of spatial-temporal clustering of KS cases, there were no significant clusters of KS cases discharged from a single institution. This implicates the need for an expanded approach to conducting spatial-temporal cluster analysis and KS surveillance given the limitations of evaluating data from a single institution.^

(Table 1) Trace element/Ca ratios of Orbulina universa shells from late Neogene Mediterranean samples

A Mediterranean composite sedimentary record was analyzed for Ba/Ca ratios on carbonate shells of Orbulina universa planktonic foraminifer (Ba/Ca)carb providing the opportunity to study and assess the extent of freshwater inputs on the basin and possible impacts on its dynamics during the Tortonian to Recent period. A number of scanning electron microscope analyses and auxiliary trace element measurements (Mn, Sr, and Mg), obtained from the same samples, exclude important diagenetic effects on the studied biogenic carbonates and corroborate the reliability of (Ba/Ca)carb ratios in foraminifera calcite as indicators of seawater source components during the studied interval. A long-term trend with (Ba/Ca)carb values shifting from ~7 to 3 µmol/mol from the base of the Tortonian to the top of the Messinian is observed. The interval of the late Messinian salinity crisis, where biogenic carbonates are missing or strongly diagenized, represents a crucial passage not monitored in our record. At the base of the Pliocene, up to about 4.7 Ma, the (Ba/Ca)carb record shows a decreasing trend from ~4 µmol/mol stabilizing itself to an about constant value of 0.9 ± 0.3 µmol/mol for the whole Plio-Pleistocene interval. These results suggest a dramatic change in the continental runoff values, up to ~3-16 times higher during part of the late Neogene (Tortonian-early Pliocene), with a possible profound modification in the physical dynamics of the Mediterranean basin. First-order mass balance equations used to estimate barium and salinity budgets in the Mediterranean Sea during the late Miocene-early Pliocene interval support the hypothesis of an active connection of the basin with the Paratethys region and of a definitive restriction at the base of the Pliocene after about 0.7 Ma from the well-known Messinian Lagomare phase. They also open intriguing scenarios on possible circulation shifts during the Neogene.

Aggregates feeding and pellet production from Microsetella norvegica collected during METEOR cruise M87/1 in Aril 2012

Harpacticoid Microsetella norvegica was fed with 5 concentrations of aggregates, collected from the station 1 (experiment 1) or from station 2 (experiment 2). The aggregates at station 1 were of phytoplankton origin and consisted mainly of Phaeocystis sp. and radiolarians; aggregates at station 2 were detritus collected from deep Mocness tows. M. norvegica was starved in filtered sea water for > 12 h, after which it was incubated together with aggregates for 8 h. After the incubation, pellets were counted and Microsetella and remaining aggregates were counted and measured. Pellet production of M. norvegica reflects feeding so that when pellet production is plotted against aggregate concentration, a functional response can be obtained.

Diurnal egg and pellet production of Calanus finmarchicus collected during METEOR cruise M87/1 in Aril 2012

Egg and pellet production of Calanus finmarchicus was measured at 6-h intervals at all stations during the second leg of the cruise. Calanus was collected at the surface 150-m using a WP2 plankton net, and incubated in chl-max water for 24-h. Each 6 hours females were transferred to a new food solution and eggs and pellets were counted. In the end of the experiment, females were measured for prosome length. The purpose of the exercise was to calculate the minimum carbon consumption of Calanus, and how large proportion of ingestion is egested as fast sinking fecal pellets, and when.

Ex situ respiration rates measured in water column samples during the METEOR cruise M87/1 in April 2012

Oxygen concentration and rate of change of oxygen were measured using the Unisense Oxygen Microsensor System. Water from different depth was taken from CTD attached niskin bottle. Measurements were conducted in 2 ml vials provided by Unisense and lasted for a minimum of two minutes after a stable rate was achieved. The sampling interval was 6 seconds. Transport containers, tubes and vials for measurements were covered with light proof black foil for dark-measurements. Measurements labeled "unfiltered" were passed through a 200 µm sieve in order to remove potential biases stemming from individual meso-zooplankton. Measurements labeled "filtered" were passed through a 0.8 µm polycarbonate filter placed on top of a wetted GF/F filter.

Lenght measurements and carbon biomass of individual zooplankton from METEOR cruise M87/1 in April 2012

Zooplankton samples were taken in five depth strata using a Multinet type Midi, with 50 µm nets. The samples were taken during the second leg only, three times at station 1, two times at station 2 and once at station 3. Zooplankton were identified to species / genus and life-stage, and at least 300 individuals were counted per sample. 10 individuals of each stage / species were measured and the numbers of eggs counted.

Zooplankton egg counts from METEOR cruise M87/1 in April 2012

Zooplankton samples were taken in five depth strata using a Multinet type Midi, with 50 µm nets. The samples were taken during the second leg only, three times at station 1, two times at station 2 and once at station 3. Zooplankton were identified to species / genus and life-stage, and at least 300 individuals were counted per sample. 10 individuals of each stage / species were measured and the numbers of eggs counted.

Zooplankton abundance from METEOR cruise M87/1 in April 2012

Zooplankton samples were taken in five depth strata using a Multinet type Midi, with 50 µm nets. The samples were taken during the second leg only, three times at station 1, two times at station 2 and once at station 3. Zooplankton were identified to species / genus and life-stage, and at least 300 individuals were counted per sample. 10 individuals of each stage / species were measured and the numbers of eggs counted.

Methylation index of Branched Tetraethers (MBT) and Cyclization ratio of Branched Tetraethers (CBT), annual mean air temperature and soil pH of sediment core GeoB6518-1 in the Congo River basin

We analyzed the distribution of branched tetraether membrane lipids derived from soil bacteria in a marine sediment record that was recovered close to the Congo River outflow, and the results enabled us to reconstruct large-scale continental temperature changes in tropical Africa that span the past 25,000 years. Tropical African temperatures gradually increased from ~21° to 25°C over the last deglaciation, which is a larger warming than estimated for the tropical Atlantic Ocean. A direct comparison with sea-surface temperature estimates from the same core revealed that the land-sea temperature difference was, through the thermal pressure gradient, an important control on central African precipitation patterns.