Thermal effects of mobile phone RF fields on children: a provocation study

The aim of this study was to examine thermal and local blood flow responses in the head area of the preadolescent boys during exposure to radiofrequency (RF) electromagnetic fields produced by a GSM mobile phone. The design was a double-blinded sham-controlled study of 26 boys, aged 14-15 years. The SAR distribution was calculated and modelled in detail. The duration of the sham periods and exposures with GSM 900 phone was 15 min each, and the tests were carried out in a climatic chamber in controlled thermoneutral conditions. The ear canal temperatures were registered from both ear canals, and the skin temperatures at several sites of the head, trunk and extremities. The local cerebral blood flow was monitored by a near-infrared spectroscopy (NIRS), and the autonomic nervous system function by recordings of ECG and continuous blood pressure. During the short-term RF exposure, local cerebral blood flow did not change, the ear canal temperature did not increase significantly and autonomic nervous system was not interfered. The strengths of this study were the age of the population, multifactorial physiological monitoring and strictly controlled thermal environment. The limitations of the study were large inter-individual variation in the physiological responses, and short duration of the exposure. Longer provocation protocols, however, might cause in children distress related confounding physiological responses.     

Spatially differing bacterial communities in water columns of the northern Baltic Sea

The Baltic Sea is a large, shallow, and strongly stratified brackish water basin. It suffers from eutrophication, toxic cyanobacterial blooms, and oxygen depletion, all of which pose a threat to local marine communities. In this study, the diversity and community structure of the northern Baltic Sea bacterial communities in the water column were, for the first time, thoroughly studied by 454 sequencing. The spring and autumn bacterial communities were one order of magnitude less diverse than those in recently studied oceanic habitats. Patchiness and strong stratification were clearly detectable; <1% of operational taxonomic units were shared among 11 samples. The community composition was more uniform horizontally (at a fixed depth) between different sites than vertically within one sampling site, implying that the community structure was affected by prevailing physical and hydrochemical conditions. Taxonomic affiliations revealed a total of 23 bacterial classes and 169 genera, while 5% of the sequences remained unclassified. The cyanobacteria accounted for <2% of the sequences, and potentially toxic cyanobacterial genera were essentially absent during the sampling seasons.     

Occupational exposure to electric fields and induced currents associated with 400 kV substation tasks from different service platforms

The aim of the study was to investigate the occupational exposure to electric fields, average current densities, and average total contact currents at 400 kV substation tasks from different service platforms (main transformer inspection, maintenance of operating device of disconnector, maintenance of operating device of circuit breaker). The average values are calculated over measured periods (about 2.5 min). In many work tasks, the maximum electric field strengths exceeded the action values proposed in the EU Directive 2004/40/EC, but the average electric fields (0.2–24.5 kV/m) were at least 40% lower than the maximum values. The average current densities were 0.1–2.3 mA/m² and the average total contact currents 2.0–143.2 µA, that is, clearly less than the limit values of the EU Directive. The average values of the currents in head and contact currents were 16–68% lower than the maximum values when we compared the average value from all cases in the same substation. In the future it is important to pay attention to the fact that the action and limit values of the EU Directive differ significantly. It is also important to take into account that generally, the workers' exposure to the electric fields, current densities, and total contact currents are obviously lower if we use the average values from a certain measured time period (e.g., 2.5 min) than in the case where exposure is defined with only the help of the maximum values. Bioelectromagnetics 32:79–83, 2011. © 2010 Wiley‐Liss, Inc.     

Faecal Microbiota Composition in Adults Is Associated with the FUT2 Gene Determining the Secretor Status

The human intestine is colonised with highly diverse and individually defined microbiota, which likely has an impact on the host well-being. Drivers of the individual variation in the microbiota compositions are multifactorial and include environmental, host and dietary factors. We studied the impact of the host secretor status, encoded by fucosyltransferase 2 (FUT2) -gene, on the intestinal microbiota composition. Secretor status determines the expression of the ABH and Lewis histo-blood group antigens in the intestinal mucosa. The study population was comprised of 14 non-secretor (FUT2 rs601338 genotype AA) and 57 secretor (genotypes GG and AG) adult individuals of western European descent. Intestinal microbiota was analyzed by PCR-DGGE and for a subset of 12 non-secretor subjects and 12 secretor subjects additionally by the 16S rRNA gene pyrosequencing and the HITChip phylogenetic microarray analysis. All three methods showed distinct clustering of the intestinal microbiota and significant differences in abundances of several taxa representing dominant microbiota between the non-secretors and the secretors as well as between the FUT2 genotypes. In addition, the non-secretors had lower species richness than the secretors. The soft clustering of microbiota into enterotypes (ET) 1 and 3 showed that the non-secretors had a higher probability of belonging to ET1 and the secretors to ET3. Our study shows that secretor status and FUT2 polymorphism are associated with the composition of human intestinal microbiota, and appears thus to be one of the key drivers affecting the individual variation of human intestinal microbiota.     

REG4 Independently Predicts Better Prognosis in Non-Mucinous Colorectal Cancer

Introduction

Colorectal cancer (CRC) is one of the world’s three most common cancers and its incidence is rising. To identify patients who benefit from adjuvant therapy requires novel biomarkers. The regenerating islet-derived gene (REG) 4 belongs to a group of small secretory proteins involved in cell proliferation and regeneration. Its up-regulated expression occurs in inflammatory bowel diseases also in gastrointestinal cancers. Reports on the association of REG4 expression with CRC prognosis have been mixed. Our aim was to investigate tumor REG4 expression in CRC patients and its coexpression with other intestinal markers.

Methods

Tumor expression of REG4 was evaluated by immunohistochemistry in 840 consecutive surgically treated CRC patients at Helsinki University Central Hospital. Expression of MUC1, MUC2, MUC5AC, synapthophysin, and chromogranin was evaluated in a subgroup of 220 consecutively operated CRC patients. REG4 expression with clinicopathological parameters, other intestinal markers, and the impact of REG4 expression on survival were assessed.

Results

REG4 expression associated with favorable clinicopathological parameters and with higher overall survival from non-mucinous CRC (p = 0.019). For such patients under 65, its expression was an independent marker of lower risk of death within 5 years that cancer; univariable hazard ratio (HR) = 0.57; 95% confidence interval (CI) (0.34–0.94); multivariable HR = 0.55; 95% CI (0.33–0.92). In non-mucinous CRC, REG4 associated with positive MUC2, MUC4, and MUC5AC expression.

Conclusion

We show, to our knowledge for the first time, that REG4 IHC expression to be an independent marker of favorable prognosis in non-mucinous CRC. Our results contradict those from studies based on quantification of REG4 mRNA levels, a discrepancy warranting further studies.     

A homogeneous single-label time-resolved fluorescence cAMP assay

G-protein-coupled receptors (GPCRs) are an important class of pharmaceutical drug targets. Functional high-throughput GPCR assays are needed to test an increasing number of synthesized novel drug compounds and their function in signal transduction processes. Measurement of changes in the cyclic adenosine monophosphate (cAMP) concentration is a widely used method to verify GPCR activation in the adenylyl cyclase pathway. Here, a single-label time-resolved fluorescence and high-throughput screening (HTS)-feasible method was developed to measure changes in cAMP levels in HEK293(i) cells overexpressing either β(2)-adrenergic or δ-opioid receptors. In the quenching resonance energy transfer (QRET) technique, soluble quenchers reduce the signal of unbound europium(III)-labeled cAMP in solution, whereas the antibody-bound fraction is fluorescent. The feasibility of this homogeneous competitive assay was proven by agonist-mediated stimulation of receptors coupled to either the stimulatory G(s) or inhibitory G(i) proteins. The reproducibility of the assays was excellent, and Z' values exceeded 0.7. The dynamic range, signal-to-background ratio, and detection limit were compared with a commercial time-resolved fluorescence resonance energy transfer (TR-FRET) assay. In both homogeneous assays, similar assay parameters were obtained when adenylyl cyclase was stimulated directly by forskolin or via agonist-mediated activation of the G(s)-coupled β(2)AR. The advantage of using the single-label approach relates to the cost-effectiveness of the QRET system compared with the two-label TR-FRET assay as there is no need for labeling of two binding partners leading to reduced requirements for assay optimization.     

VEGFR-3 controls tip to stalk conversion at vessel fusion sites by reinforcing Notch signalling

Angiogenesis, the growth of new blood vessels, involves specification of endothelial cells to tip cells and stalk cells, which is controlled by Notch signalling, whereas vascular endothelial growth factor receptor (VEGFR)-2 and VEGFR-3 have been implicated in angiogenic sprouting. Surprisingly, we found that endothelial deletion of Vegfr3, but not VEGFR-3-blocking antibodies, postnatally led to excessive angiogenic sprouting and branching, and decreased the level of Notch signalling, indicating that VEGFR-3 possesses passive and active signalling modalities. Furthermore, macrophages expressing the VEGFR-3 and VEGFR-2 ligand VEGF-C localized to vessel branch points, and Vegfc heterozygous mice exhibited inefficient angiogenesis characterized by decreased vascular branching. FoxC2 is a known regulator of Notch ligand and target gene expression, and Foxc2(+/-);Vegfr3(+/-) compound heterozygosity recapitulated homozygous loss of Vegfr3. These results indicate that macrophage-derived VEGF-C activates VEGFR-3 in tip cells to reinforce Notch signalling, which contributes to the phenotypic conversion of endothelial cells at fusion points of vessel sprouts.     

Fluctuating asymmetry as a biomarker of habitat fragmentation in an area-sensitive passerine,the Eurasian treecreeper (Certhia familiaris)

The research investigating fluctuating asymmetry (FA), a phenotypic proxy of developmental instability, as a potential early-warning biomarker of anthropogenic stress like habitat fragmentation has produced controversial results. We examined the influence of habitat fragmentation at the landscape-scale, divided into habitat amount and configuration, on feather length FA in the Eurasian treecreeper (Certhia familiaris), an area-sensitive old-growth forest passerine breeding in boreal forests that are currently under intense management. Our study included one tail and wing feather, measured in both sexes of the 14-day-old nestlings and adults. Habitat amount was measured as the proportions of suitable forest habitats and open unsuitable areas, mean patch isolation and nesting patch size whereas habitat configuration was measured as mean patch density, size and shape and edge density. We found only weak sex- and age-related associations between feather length FA and habitat fragmentation that explained just 4.9% of variance in FA. Habitat loss was associated with higher FA in males only while the habitats with low degree of configuration tended to be related to lower FA in adults only. From the biomarker perspective, FA may not thus hold a great promise as a strong and general indicator of habitat fragmentation.     

Quantifying killing of orangutans and human-orangutan conflict in Kalimantan, Indonesia

Human-orangutan conflict and hunting are thought to pose a serious threat to orangutan existence in Kalimantan, the Indonesian part of Borneo. No data existed prior to the present study to substantiate these threats. We investigated the rates, spatial distribution and causes of conflict and hunting through an interview-based survey in the orangutan's range in Kalimantan, Indonesia. Between April 2008 and September 2009, we interviewed 6983 respondents in 687 villages to obtain socio-economic information, assess knowledge of local wildlife in general and orangutan encounters specifically, and to query respondents about their knowledge on orangutan conflicts and killing, and relevant laws. This survey revealed estimated killing rates of between 750 and 1800 animals killed in the last year, and between 1950 and 3100 animals killed per year on average within the lifetime of the survey respondents. These killing rates are higher than previously thought and are high enough to pose a serious threat to the continued existence of orangutans in Kalimantan. Importantly, the study contributes to our understanding of the spatial variation in threats, and the underlying causes of those threats, which can be used to facilitate the development of targeted conservation management.     

Secretor genotype (FUT2 gene) is strongly associated with the composition of Bifidobacteria in the human intestine

Intestinal microbiota plays an important role in human health, and its composition is determined by several factors, such as diet and host genotype. However, thus far it has remained unknown which host genes are determinants for the microbiota composition. We studied the diversity and abundance of dominant bacteria and bifidobacteria from the faecal samples of 71 healthy individuals. In this cohort, 14 were non-secretor individuals and the remainders were secretors. The secretor status is defined by the expression of the ABH and Lewis histo-blood group antigens in the intestinal mucus and other secretions. It is determined by fucosyltransferase 2 enzyme, encoded by the FUT2 gene. Non-functional enzyme resulting from a nonsense mutation in the FUT2 gene leads to the non-secretor phenotype. PCR-DGGE and qPCR methods were applied for the intestinal microbiota analysis. Principal component analysis of bifidobacterial DGGE profiles showed that the samples of non-secretor individuals formed a separate cluster within the secretor samples. Moreover, bifidobacterial diversity (p<0.0001), richness (p<0.0003), and abundance (p<0.05) were significantly reduced in the samples from the non-secretor individuals as compared with those from the secretor individuals. The non-secretor individuals lacked, or were rarely colonized by, several genotypes related to B. bifidum, B. adolescentis and B. catenulatum/pseudocatenulatum. In contrast to bifidobacteria, several bacterial genotypes were more common and the richness (p<0.04) of dominant bacteria as detected by PCR-DGGE was higher in the non-secretor individuals than in the secretor individuals. We showed that the diversity and composition of the human bifidobacterial population is strongly associated with the histo-blood group ABH secretor/non-secretor status, which consequently appears to be one of the host genetic determinants for the composition of the intestinal microbiota. This association can be explained by the difference between the secretor and non-secretor individuals in their expression of ABH and Lewis glycan epitopes in the mucosa.