Binding Affinity,Specificity and Comparative Biodistribution of the Parental Murine Monoclonal Antibody MX35 (Anti-NaPi2b) and Its Humanized Version Rebmab200

The aim of this preclinical study was to evaluate the characteristics of the monoclonal antibody Rebmab200, which is a humanized version of the ovarian-specific murine antibody MX35. This investigation contributes to the foundation for future clinical α-radioimmunotherapy of minimal residual ovarian cancer with ²¹¹At-Rebmab200. Here, the biodistribution of ²¹¹At-Rebmab200 was evaluated, as was the utility of ^99mTc-Rebmab200 for bioimaging. Rebmab200 was directly compared with its murine counterpart MX35 in terms of its in-vitro capacity for binding the immobilized NaPi2B epitope and live cells; we also assessed its biodistribution in nude mice carrying subcutaneous OVCAR-3 tumors. Tumor antigen and cell binding were similar between Rebmab200 and murine MX35, as was biodistribution, including normal tissue uptake and in-vivo tumor binding. We also demonstrated that ^99mTc-Rebmab200 can be used for single-photon emission computed tomography of subcutaneous ovarian carcinomas in tumor-bearing mice. Taken together, our data support the further development of Rebmab200 for radioimmunotherapy and diagnostics.     

Time Trends in Incidence and Mortality of Acute Myocardial Infarction,and All-Cause Mortality following a Cardiovascular Prevention Program in Sweden

Background

In 1988, a cardiovascular prevention program which combined an individual and a population-based strategy was launched within primary health-care in Sollentuna, a municipality in Stockholm County. The aim of this study was to investigate time trends in the incidence of and mortality from acute myocardial infarction and all-cause mortality in Sollentuna compared with the rest of Stockholm County during a period of two decades following the implementation of a cardiovascular prevention program.

Materials and Methods

The average population in Sollentuna was 56,589 (49% men) and in Stockholm County (Sollentuna included) 1,795,504 (49% men) during the study period of 1987–2010. Cases of hospitalized acute myocardial infarction and death were obtained for the population of Sollentuna and the rest of Stockholm County using national registries of hospital discharges and deaths. Acute myocardial infarction incidence and mortality were estimated using the average population of Sollentuna and Stockholm in 1987–2010.

Results

During the observation period, the incidence of acute myocardial infarction decreased more in Sollentuna compared with the rest of Stockholm County in women (-22% vs. -7%; for difference in slope <0.05). There was a trend towards a greater decline in Sollentuna compared to the rest of Stockholm County in the incidence of acute myocardial infarction (in men), acute myocardial mortality, and all-cause mortality but the differences were not significant.

Conclusion

During a period of steep decline in acute myocardial infarction incidence and mortality in Stockholm County the municipality of Sollentuna showed a stronger trend in women possibly compatible with favorable influence of a cardiovascular prevention program.

Trial Registration

ClinicalTrials.gov NCT02212145     

Environmental benefits from reusing clothes

Background, aim, and scope  

Clothes are often discarded when much of their potential lifetime is left. Many charitable organizations therefore collect used clothing and resell it as second-hand clothes for example in Eastern Europe or Africa. In this connection, the question arises whether reusing clothes actually results in a decrease of the environmental burden of the life cycle of clothing. The environmental burden of clothing has been studied in several studies. However, most of these studies focus solely on the energy consumption aspects and pay little attention to the potential benefits of diverting used clothing from the waste stream. The aim of the study was to assess the net environmental benefits brought by the disposal of used clothing through charities who return them for second-hand sales assuming that second-hand clothes to some extent replace the purchase of new clothes.     

Temperature as a predictor of survival of the pine processionary moth in the Italian Alps

1 The pine processionary moth Thaumetopoea pityocampa is expanding its geographical range in Europe, as a consequence of enhanced winter survival under a warmer climate. A combination of daytime nest temperatures and night air temperatures determines the number of hours larvae are able to feed (hours above realized feeding threshold, RFT). 2 We tested the RFT‐based model for survival across multiple areas of the insect’s range in the Italian Alps over a 2‐year period. In a series of translocation experiments using natural temperature gradients as spatial analogues for global warming, we transferred colonies of T. pityocampa larvae to sites within zones of historical distribution, recent distribution, and outside the present range. The sites included traditional (Pinus nigra, Pinus sylvestris) as well as novel (Pinus mugo, Pinus uncinata, Pinus cembra) hosts. 3 Survival during precold (August to November), cold (December to February) and postcold (March to May) periods were analysed against climatic variables (temperature and rainfall) and predictors developed by the model. 4 Host species did not significantly affect final survival, with the exception of slower larval development, and resulting lower cold tolerance, on P. cembra than on P. mugo at the same site. 5 Across all the sites and hosts, final survival of colonies depended on the number of feeding hours during the cold period (RFT), which explained 82% of the variance in a regression model. We recommend using RFT, or its surrogate daily mean minimum temperature when nest temperature is not available, in predictive models of range expansion of T. pityocampa under climate change scenarios.     

Polar night ecology of a pelagic predator,the chaetognath <Emphasis Type="Italic">Parasagitta elegans</Emphasis>

The annual routines and seasonal ecology of herbivorous zooplankton species are relatively well known due to their tight coupling with their pulsed food source, the primary production. For higher trophic levels of plankton, these seasonal interactions are less well understood. Here, we study the mid-winter feeding of chaetognaths in high-Arctic fjord ecosystems. Chaetognaths are planktivorous predators which comprise high biomass in high-latitude seas. We investigated the common species Parasagitta elegans around the Svalbard archipelago (78–81°N) during the winters of 2012 and 2013. Our samples consisted of individuals (body lengths 9–55 mm) from three fjords, which were examined for gut contents (n = 903), stable isotopes, fatty acid composition, and maturity status (n = 352). About a quarter of the individuals contained gut contents, mainly lipid droplets and chitinous debris, whilst only 4 % contained identifiable prey, chiefly the copepods Calanus spp. and Metridia longa. The δ¹⁵N content of P. elegans, and its average trophic level of 2.9, confirmed its carnivorous position and its fatty acid profile [in particular its high levels of 20:1(n-9) and 22:1(n-11)] confirmed carnivory on Calanus. Observations of undeveloped gonads in many of the larger P. elegans, and the absence of small individuals <10 mm, suggested that reproduction had not started this early in the year. Its average feeding rate across fjords and years was 0.12 prey ind.^?1 day^?1, which is low compared to estimates of spring and summer feeding in high-latitude environments. Our findings suggest reduced feeding activity during winter and that predation by P. elegans had little impact on the mortality of copepods.     

Non-indigenous signal crayfish <Emphasis Type="Italic">Pacifastacus leniusculus</Emphasis> are now common in Danish streams: preliminary status for national distribution and protective actions

North American signal crayfish (Pacifastacus leniusculus) are invasive in Europe and pose a serious threat to indigenous European crayfish such as the noble crayfish (Astacus astacus). This is mainly because signal crayfish is the carrier of crayfish plague agent, Aphanomyces astaci, which freshwater crayfish from all other continents are highly susceptible to. Until recently, the distribution of signal crayfish in Danish streams has been considered local and restricted to a small geographical area. Here we present data demonstrating that signal crayfish are now widespread in Denmark, including the largest Danish river, River Gudenå. For one of the rivers where co-existing signal crayfish and indigenous noble crayfish were documented, sensitive molecular tests could not detect the crayfish plague agent Aphanomyces astaci in either species. Hence, it seems that not all signal crayfish are chronic carriers of the disease. For the remaining freshwater systems with the introduced signal crayfish, the infection status is presently unknown. Large areas of the freshwater systems in Denmark also remain unexplored with respect to presence/absence of signal crayfish and noble crayfish. Nevertheless, our preliminary data that covers about 14% of the Danish rivers, strongly suggests that signal crayfish should be considered as a common invader that poses an increased threat to the biota in Danish streams, in particular for the indigenous noble crayfish.     

Hierarchical Cluster-based Partial Least Squares Regression (HC-PLSR) is an efficient tool for metamodelling of nonlinear dynamic models

Background

Network inference methods reconstruct mathematical models of molecular or genetic networks directly from experimental data sets. We have previously reported a mathematical method which is exclusively data-driven, does not involve any heuristic decisions within the reconstruction process, and deliveres all possible alternative minimal networks in terms of simple place/transition Petri nets that are consistent with a given discrete time series data set.

Results

We fundamentally extended the previously published algorithm to consider catalysis and inhibition of the reactions that occur in the underlying network. The results of the reconstruction algorithm are encoded in the form of an extended Petri net involving control arcs. This allows the consideration of processes involving mass flow and/or regulatory interactions. As a non-trivial test case, the phosphate regulatory network of enterobacteria was reconstructed using in silico-generated time-series data sets on wild-type and in silico mutants.

Conclusions

The new exact algorithm reconstructs extended Petri nets from time series data sets by finding all alternative minimal networks that are consistent with the data. It suggested alternative molecular mechanisms for certain reactions in the network. The algorithm is useful to combine data from wild-type and mutant cells and may potentially integrate physiological, biochemical, pharmacological, and genetic data in the form of a single model.     

Oceanography and Marine Environment of the Basque Country. Elsevier Oceanography Series 70. Edited by A. Borja and M. Collins (2004) Elsevier B.V., Amsterdam. ISBN 0-444-51581-X. ISSN 0422-9894 (Series).

This is not a book that you probably start reading from thefirst page. Its 24 review chapters have informative titles andare organised in seven sections that together with a four-pagelocation index and an eight-page subject index invites you todive for your favourite subjects. The editors have succeededto structure the book in ways that makes easy navigation amongstits     

Regional myocardial work by strain Doppler echocardiography and LV pressure: a new method for quantifying myocardial function

There is a need for better methods to quantify regional myocardial function. In the present study, we investigated the feasibility of quantifying regional function in terms of a segmental myocardial work index as derived from strain Doppler echocardiography (SDE) and invasive pressure. In 10 anesthetized dogs, we measured left ventricular (LV) pressure by micromanometer and myocardial longitudinal strains by SDE and sonomicrometry. The regional myocardial work index (RMWI) was calculated as the area of the pressure-strain loop. As a reference method for strain, we used sonomicrometry. By convention, the loop area was assigned a positive sign when the pressure-strain coordinates rotated counterclockwise. Measurements were done at baseline and during volume loading and left anterior descending coronary artery (LAD) occlusion, respectively. There was a good correlation between RMWI calculated from strain by SDE and strain by sonomicrometry (y = 0.73x + 0.21, r = 0.82, P < 0.01). Volume loading caused an increase in RMWI from 1.3 +/- 0.2 to 2.2 +/- 0.1 kJ/m3 (P < 0.05) by SDE and from 1.5 +/- 0.3 to 2.7 +/- 0.3 kJ/m3 (P = 0.066) by sonomicrometry. Short-term ischemia (1 min) caused a decrease in RMWI from 1.3 +/- 0.2 to 0.3 +/- 0.04 kJ/m3 (P < 0.05) and from 1.3 +/- 0.3 to 0.5 +/- 0.2 kJ/m3 (P < 0.05) by SDE and sonomicrometry, respectively. In the nonischemic ventricle and during short-term ischemia, the pressure-strain loops rotated counterclockwise, consistent with actively contracting segments. Long-term ischemia (3 h), however, caused the pressure-strain loop to rotate clockwise, consistent with entirely passive segments, and the loop areas became negative, -0.2 +/- 0.1 and -0.1 +/- 0.03 kJ/m3 (P < 0.05) by SDE and sonomicrometry, respectively. A RMWI can be estimated by SDE in combination with LV pressure. Furthermore, the orientation of the loop can be used to assess whether the segment is active or passive.