Are mouse lens epithelial cells more sensitive to γ-irradiation than lymphocytes?

In this pilot study we compared for the first time the radiation sensitivity of mouse lens epithelial cells (LECs) and mouse lymphocytes. We freshly prepared LECs and lymphocytes and irradiated them with γ-rays (¹³⁷Cs; doses ranging from 0.25 to 2 Gy). DNA damage and repair were evaluated by alkaline comet assay and γH2AX foci assay. Using the comet assay, we observed a dose-dependent increase in DNA damage in both cell types. The faster formation of single- and double-strand breaks in LECs of C57BL/6 mice at doses below 1 Gy needs to be confirmed in other mouse strains. Immunofluorescence for γH2AX foci showed a higher degree of lesions in LECs from C57BL/6J mice compared to those of JF1 mice and to lymphocytes of both strains. Correspondingly, repair of DNA damage proceeded faster in LECs of C57BL/6J mice compared to LECs of JF1 mice and lymphocytes of both strains. It is obvious that the lymphocytes of both strains repaired DNA lesions more slowly than the corresponding LECs. In conclusion, our results demonstrate that LECs of C57Bl/6 mice show a steeper dose–response than lymphocytes in both types of experiments. It shows that both test systems are able to be used also at doses below 0.25 Gy. The observed difference in DNA repair between the LECs from C57BL/6J mice compared to the LECs from JF1 mice and to the lymphocytes of both strains warrants further experiments to identify the underlying molecular mechanisms.     

Is it going to be SIN?

Insertional mutagenesis resulting in a leukaemia-like lymphoproliferative disease, as observed in the X-SCID (severe combined immunodeficiency) clinical trial using a gamma-retroviral vector that transferred a functional copy of the defective gene into hematopoietic precursor cells of affected children, sparked a debate about a ban on conventional gamma-retroviral vectors. This commentary summarizes the relevant data on this topic and concludes that there is no preclinical or clinical evidence as yet that SIN vectors, which self-inactivate the retroviral long terminal repeats (LTRs), will indeed show an improved safety profile. Conventional murine leukaemia virus (MLV) vectors can thus be used further in clinical gene therapy trials but require a thorough case-by-case risk-benefit analysis.     

Computational genetics: from mouse to human?

In this article, we describe a novel computational-analysis method that rapidly identified the genetic basis for several trait differences among inbred mouse strains. This approach enables researchers to identify a causative genetic factor by correlating a pattern of observable physiological or pathological differences among selected inbred strains with a pattern of genetic variation. Compared with conventional methods used for mouse genetic analysis, which require many years to produce results, this haplotype-based computational analysis can be rapidly performed. We discuss the factors affecting the performance and precision of this computational method. Although it currently can analyze traits of limited genetic complexity in mouse, the potential application of this genetic-analysis method to other experimental organisms, and possibly humans, is evaluated.     

Are traits measured on pot grown plants representative of those in natural communities?

Question: The quantification of functional traits in natural communities can be difficult (e.g. root traits, RGR). Can functional traits measured on pot grown plants be reliably applied to natural communities? Alternatively, can below‐ground plant traits be predicted from above‐ground traits? Location: Southeastern Australia. Methods: We compared 17 shoot, root and whole‐plant morphological traits measured on 14 plant species in a native grassland community to those measured under two different pot conditions: unfertilised and fertilised. Results: The majority of trait values for pot grown plants differed to plants in the field, however, species ranking remained consistent for most leaf traits between the field and the two pot growing conditions. In contrast, species ranking was not consistent for most whole plant traits when comparing field plants to fertilised pot grown plants, providing a caution against the tendency to grow plants in controlled conditions at ‘optimal’ (high) resource levels. Moderate to strong correlations were found between below‐ground and above‐ground plant traits, including between root dry matter content and leaf dry matter content, and between specific root area and specific leaf area. Conclusions: The utility of pot grown plants to quantify traits for field plants is highly dependent on the selection of the growing conditions in the controlled environment. The consistency we observed between above‐ground and below‐ground trait strategies suggests that below‐ground traits may be predictable based on above‐ground traits, reducing the need to quantify root traits on cultured plants.     

Are Statistical Contributions to Medicine Undervalued?

Econometricians Daniel McFadden and James Heckman won the 2000 Nobel Prize in economics for their work on discrete choice models and selection bias. Statisticians and epidemiologists have made similar contributions to medicine with their work on case-control studies, analysis of incomplete data, and causal inference. In spite of repeated nominations of such eminent figures as Bradford Hill and Richard Doll, however, the Nobel Prize in physiology and medicine has never been awarded for work in biostatistics or epidemiology. (The "exception who proves the rule" is Ronald Ross, who, in 1902, won the second medical Nobel for his discovery that the mosquito was the vector for malaria. Ross then went on to develop the mathematics of epidemic theory--which he considered his most important scientific contribution-and applied his insights to malaria control programs.) The low esteem accorded epidemiology and biostatistics in some medical circles, and increasingly among the public, correlates highly with the contradictory results from observational studies that are displayed so prominently in the lay press. In spite of its demonstrated efficacy in saving lives, the "black box" approach of risk factor epidemiology is not well respected. To correct these unfortunate perceptions, statisticians would do well to follow more closely their own teachings: conduct larger, fewer studies designed to test specific hypotheses, follow strict protocols for study design and analysis, better integrate statistical findings with those from the laboratory, and exercise greater caution in promoting apparently positive results.     

Are aromatase inhibitors superior to antiestrogens?

Aromatase inhibitors (AIs) have been in use to treat metastatic breast cancer for over 25 years. Recently potent and specific AIs have been introduced, which, because of their low toxicity profile, are being used in the adjuvant and neoadjuvant situation and also for the prevention of breast cancer. The two non-steroidal AIs, anastrozole and letrozole, and the steroidal AI, exemestane, have all shown superiority to tamoxifen as first-line treatment for advanced breast cancer. Interestingly, the oestrogen receptor downregulator, fulvestrant, was shown to be equivalent to anastrozole when compared as second-line therapy after the failure of tamoxifen. The first adjuvant AI trial began in 1996 and recruited over 9000 patients (ATAC trial). Anastrozole was compared with tamoxifen and a combination of the two drugs. There were no significant differences between tamoxifen and the combination. However, anastrozole showed about a 20% improvement in disease-free survival in ER+ disease compared with the other treatments. An overall survival analysis will be reported later this year. Two trials have compared 5 years of tamoxifen with 2–3 years of tamoxifen, followed by 2–3 years of AI (one trial (ITA) used anastrozole and another (intergroup) exemestane). Both trials show a disease-free advantage for the switch to AI. In another study (MA17) 5 years of tamoxifen was followed by a randomisation to letrozole or placebo and showed a significant disease-free advantage to the AI. Both letrozole and anastrozole show superiority to tamoxifen when used as a neoadjuvant therapy. Anastrozole significantly reduced contralateral breast cancer compared with tamoxifen, and this has led to two prevention trials: one in women at risk comparing anastrozole with placebo and the other after excision of DCIS comparing anastrozole with tamoxifen (IBIS II). The NCI Canada has also just initiated a trial of exemestane for prevention. Nearly all data available indicate that AIs are superior to tamoxifen. The important question is whether survival is improved when they are used as adjuvant therapy?     

Are Robertsonian variations a frequent phenomenon in mouse populations in Eurasia?

We examined the karyotypes of 212 specimens of the house mouse obtained from 44 localities in central and eastern Europe, and several regions of Asia. The Robertsonian chromosome fusion 5.12 was found in a population of Mus musculus musculus in Czechoslovakia. Two large HSRs on chromosome 1 were ascertained in four female mice from western Siberia. In most of the localities under study, the mice possessed a normal karyotype with 40 acrocentric chromosomes.     

Are ubiquitination pathways central to Parkinson's disease?

Parkinson's disease (PD) is the most common neurodegenerative movement disorder. The major motor disabilities of PD are associated with the extensive loss of dopaminergic neurons in the substantia nigra pars compacta. The physiological changes and biochemical pathways involved in the selective demise of these neurons are still unclear. Recent studies have demonstrated that alterations or reductions in ubiquitin-mediated proteasome function can be causal of at least some forms of parkinsonism, and multiple lines of evidence suggest that this mechanism of protein degradation may play an important role in the etiology of PD.     

MITOCHONDRIA: Are mitochondria accessory to metastasis?

Since the nineteenth century the importance of mitochondria in cellular physiology has been growing steadily. Not only the organelle harbors the main systems for ATP generation, but also buffers the redox potential in the cytosol and is one of the protagonists of the intrinsic pathway for apoptosis. In tumor cells, mitochondria went from being dysfunctional compartments to playing a supportive or perhaps even a triggering part in metastasis. This “Organelle In Focus” article discusses the classical metabolic events that occur in mitochondria and why these pathways could be essential for the onset of the malignant phenotype. Finally, we propose that the oxidative metabolism of tumor cells in conjunction with the inactivation of anoikis may have been coopted through a non-adaptive evolutionary process.     

Are coelenterate cells permeable to large anions?

• 1.1. Substitution of chloride by isethionate, a bulky anion, did not modify the intracellular cation or water content in cells of tentacles, and only slightly decreased sodium content in body wall cells of the coelenterate Condylactis gigantea, in contrast with the appreciable reductions expected in the case of impenneant anions.
• 2.2. As isethionic acid is a strong acid, the salt should be almost totally ionized at the pH of seawater (8.6) and at the presumably close to neutral intracellular pH. Therefore, the anion, rather than the undissociated acid, would appear to be the permeating species.
• 3.3. Isethionate ion appears to distribute across the cell membrane as does chloride: according to the transmembrane potential difference.

     

Are Unfamiliar Neighbours Considered to Be Dear-Enemies?

Background

Discriminating threatening individuals from non-threatening ones allow territory owners to modulate their territorial responses according to the threat posed by each intruder. This ability reduces costs associated with territorial defence. Reduced aggression towards familiar adjacent neighbours, termed the dear-enemy effect, has been shown in numerous species. An important question that has never been investigated is whether territory owners perceive distant neighbours established in the same group as strangers because of their unfamiliarity, or as dear-enemies because of their group membership.

Methodology/Principal Findings

To investigate this question, we played back to male skylarks (Alauda arvensis) songs of adjacent neighbours, distant neighbours established a few territories away in the same microdialect area and strangers. Additionally, we carried out a propagation experiment to investigate how far skylark songs are propagated in their natural habitat and we estimated repertoire similarity between adjacent neighbours, distant neighbours and strangers. We show that skylarks, in the field, respond less aggressively to songs of their distant and likely unfamiliar neighbours, as shown by the propagation experiment, compared to stranger songs. The song analysis revealed that individuals share a high amount of syllables and sequences with both their adjacent and distant neighbours, but only few syllables and no sequences with strangers.

Conclusions

The observed reduction of aggression between distant neighbours thus probably results from their familiarity with the vocal group signature shared by all members of the neighbourhood. Therefore, in skylarks, dear-enemy-like relationships can be established between unfamiliar individuals who share a common acoustic code.