Methyl farnesoate binding proteins in tissues of the spider crab, Libinia emarginata

Methyl farnesoate (MF) binding proteins (MFBPs) were found in the ovaries, testes, accessory glands, and hemolymph of the spider crab Libinia emarginata, by photoaffinity labeling the tissues in vitro with tritiated farnesyl diazomethyl ketone ([3H]-FDK). Specificity was demonstrated by competitive displacement of [3H]-FDK with MF. SDS-PAGE followed by fluorography revealed several labeled proteins in the hemolymph and testes with molecular masses ranging from 29 to 116 kDa, and two in the ovary that were 97 and 70 kDa. Tissues from reproductive animals bound twice as much label per gram weight compared to those that were from non-reproductive crabs.     

Dimethyl Fumarate Inhibits the Nuclear Factor κB Pathway in Breast Cancer Cells by Covalent Modification of p65 Protein

In breast tumors, activation of the nuclear factor κB (NFκB) pathway promotes survival, migration, invasion, angiogenesis, stem cell-like properties, and resistance to therapy—all phenotypes of aggressive disease where therapy options remain limited. Adding an anti-inflammatory/anti-NFκB agent to breast cancer treatment would be beneficial, but no such drug is approved as either a monotherapy or adjuvant therapy. To address this need, we examined whether dimethyl fumarate (DMF), an anti-inflammatory drug already in clinical use for multiple sclerosis, can inhibit the NFκB pathway. We found that DMF effectively blocks NFκB activity in multiple breast cancer cell lines and abrogates NFκB-dependent mammosphere formation, indicating that DMF has anti-cancer stem cell properties. In addition, DMF inhibits cell proliferation and significantly impairs xenograft tumor growth. Mechanistically, DMF prevents p65 nuclear translocation and attenuates its DNA binding activity but has no effect on upstream proteins in the NFκB pathway. Dimethyl succinate, the inactive analog of DMF that lacks the electrophilic double bond of fumarate, is unable to inhibit NFκB activity. Also, the cell-permeable thiol N-acetyl l-cysteine, reverses DMF inhibition of the NFκB pathway, supporting the notion that the electrophile, DMF, acts via covalent modification. To determine whether DMF interacts directly with p65, we synthesized and used a novel chemical probe of DMF by incorporating an alkyne functionality and found that DMF covalently modifies p65, with cysteine 38 being essential for the activity of DMF. These results establish DMF as an NFκB inhibitor with anti-tumor activity that may add therapeutic value in the treatment of aggressive breast cancers.     

Tawny owl prey remains indicate differences in the dynamics of coastal and inland vole populations in southern Finland

Some studies suggest that mild winters decrease overwinter survival of small mammals or coincide with decreased cyclicity in vole numbers, whereas other studies suggest non-significant or positive relationships between mild winter conditions and vole population dynamics. We expect for the number of voles to be higher in the rich and low-lying habitats of the coastal areas than in the less fertile areas inland. We assume that this geographical difference in vole abundances is diminished by mild winters especially in low-lying habitats. We examine these relationships by generalized linear mixed models using prey remains of breeding tawny owls Strix aluco as a proxy for the abundance of voles. The higher number of small voles in the coastal area than in the inland area suggest that vole populations were denser in the coastal area. Vole populations of both areas were affected by winter weather conditions particularly in March, but these relationships differed between areas. The mild ends of winter with frequent fluctuations of the ambient temperature around the freezing point (“frost seesaw”) constrained significantly the coastal vole populations, while deep snow cover, in general after hard winters, was followed by significantly lowered number of voles only in the inland populations. Our results suggest that coastal vole populations are more vulnerable to mild winters than inland ones. We also show that tawny owl prey remains can be used in a meaningful way to study vole population dynamics.     

Exposure classification of MRI workers in epidemiological studies

We estimate that there are about 100,000 workers from different disciplines, such as radiographers, nurses, anesthetists, technicians, engineers, etc., who can be exposed to substantial electromagnetic fields (compared to normal background levels) around magnetic resonance imaging (MRI) scanners. There is a need for well‐designed epidemiological studies of MRI workers but since the exposure from MRI equipment is a very complex mixture of static magnetic fields, switched gradient magnetic fields, and radiofrequency electromagnetic fields (RF EMF), it is necessary to discuss how to assess the exposure in epidemiological studies. As an alternative to the use of job title as a proxy of exposure, we propose an exposure categorization for the different professions working with MRI equipment. Specifically, we propose defining exposure in three categories, depending on whether people are exposed to only the static field, to the static plus switched gradient fields or to the static plus switched gradient plus RF fields, as a basis for exposure assessment in epidemiological studies. Bioelectromagnetics 34:81–84, 2013. © 2012 Wiley Periodicals, Inc.     

Fast direct melting of brackish sea-ice samples results in biologically more accurate results than slow buffered melting

Sea-ice samples intended for biological analyses, e.g., chlorophyll-a, cell enumeration of algae and protozoa and primary production, are affected by the sampling and sample processing methods. In this study, we compared different sample processing methods by melting Baltic Sea ice samples in different ways (direct melting, buffered melting in filtered seawater (FSW) and buffered melting in artificial seawater at two different salinities with added nutrients) at two temperatures [+4 °C and room temperature (RT)]. We show that sea-ice samples intended for most commonly used biological analyses can be melted without the addition of FSW. In particular, adding artificial seawater should be avoided. To minimize biological processes, such as growth, death, predation and pigment degradation, the melting should be done rapidly at RT preferably by gently shaking the sample to keep the melt cool.     

Inhibition of PI3-kinase-Akt pathway enhances dexamethasone-induced apoptosis in a human follicular lymphoma cell line

Glucocorticoids are commonly used in the treatment of various lymphoid malignancies. In the present study, we show that dexamethasone (Dex) induced depolarization of mitochondrial membrane, release of cytochrome c and DNA fragmentation in a human follicular lymphoma cell line, HF28RA. New protein synthesis was required before Dex-induced mitochondrial changes, and the kinetics of the apoptotic events correlated with the upregulation of the Bim protein. Furthermore, we studied whether specific inhibitors of known survival pathways would potentiate Dex-induced apoptosis. Our results show that inhibition of PKC and ERK pathways had no effect on apoptosis. In contrast, inhibition of PI3-kinase or Akt markedly enhanced Dex-induced apoptosis. The enhancement was seen at the mitochondrial level, and the kinetics of apoptosis was notably accelerated. In addition, inhibition of PI3-kinase did not alter levels of Bax, Bcl-2, Bcl-X(L) or Bim proteins in mitochondria but caused translocation of the pro-apoptotic protein Bad to mitochondria. However, inhibition of PI3-kinase-Akt pathway and subsequent translocation of Bad to mitochondria did not induce apoptosis itself. Based on these results and our current understanding of Bim and Bad action, it seems that both proteins play a synergistic role in this process. Thus, these results indicate that inhibitors of PI3-kinase-Akt pathway might be combined in future with glucocorticoids to improve the treatment of lymphoid malignancies.     

Horizontal Gene Transfer of PIB-Type ATPases among Bacteria Isolated from Radionuclide- and Metal-Contaminated Subsurface Soils

Aerobic heterotrophs were isolated from subsurface soil samples obtained from the U.S. Department of Energy's (DOE) Field Research Center (FRC) located at Oak Ridge, Tenn. The FRC represents a unique, extreme environment consisting of highly acidic soils with cooccurring heavy metals, radionuclides, and high nitrate concentrations. Four hundred isolates obtained from contaminated soil were assayed for heavy metal resistance, and a smaller subset was assayed for tolerance to uranium. The vast majority of the isolates were gram-positive bacteria and belonged to the high-G+C- and low-G+C-content genera Arthrobacter and Bacillus, respectively. Genomic DNA from a randomly chosen subset of 50 Pb-resistant (Pb^r) isolates was amplified with PCR primers specific for P_IB-type ATPases (i.e., pbrA/cadA/zntA). A total of 10 pbrA/cadA/zntA loci exhibited evidence of acquisition by horizontal gene transfer. A remarkable dissemination of the horizontally acquired P_IB-type ATPases was supported by unusual DNA base compositions and phylogenetic incongruence. Numerous Pb^r P_IB-type ATPase-positive FRC isolates belonging to the genus Arthrobacter tolerated toxic concentrations of soluble U(VI) (UO₂²⁺) at pH 4. These unrelated, yet synergistic, physiological traits observed in Arthrobacter isolates residing in the contaminated FRC subsurface may contribute to the survival of the organisms in such an extreme environment. This study is, to the best of our knowledge, the first study to report broad horizontal transfer of P_IB-type ATPases in contaminated subsurface soils and is among the first studies to report uranium tolerance of aerobic heterotrophs obtained from the acidic subsurface at the DOE FRC.     

Psychophysiological tests and provocation of subjects with mobile phone related symptoms

The aim of the present study was to investigate the effect of exposure to a mobile phone-like radiofrequency (RF) electromagnetic field on persons experiencing subjective symptoms when using mobile phones (MP). Twenty subjects with MP-related symptoms were recruited and matched with 20 controls without MP-related symptoms. Each subject participated in two experimental sessions, one with true exposure and one with sham exposure, in random order. In the true exposure condition, the test subjects were exposed for 30 min to an RF field generating a maximum SAR(1g) in the head of 1 W/kg through an indoor base station antenna attached to a 900 MHz GSM MP. The following physiological and cognitive parameters were measured during the experiment: heart rate and heart rate variability (HRV), respiration, local blood flow, electrodermal activity, critical flicker fusion threshold (CFFT), short-term memory, and reaction time. No significant differences related to RF exposure conditions were detected. Also no differences in baseline data were found between subject groups, except for the reaction time, which was significantly longer among the cases than among the controls the first time the test was performed. This difference disappeared when the test was repeated. However, the cases differed significantly from the controls with respect to HRV as measured in the frequency domain. The cases displayed a shift in low/high frequency ratio towards a sympathetic dominance in the autonomous nervous system during the CFFT and memory tests, regardless of exposure condition. This might be interpreted as a sign of differences in the autonomous nervous system regulation between persons with MP related subjective symptoms and persons with no such symptoms.