Homing in on intracellular Abeta?

In this issue of Neuron, a study by Billings et al. points to intracellular Abeta as a possible cause of neuronal dysfunction. In a mouse model of Alzheimer's disease, Billings et al. link appearance of intraneuronal Abeta to cognitive impairments and then show that "clearance" of intraneuronal Abeta by anti-Abeta antibodies restores cognitive deficits.     

Centriole duplication: centrin in on answers?

Many aspects of centriole biology remain mysterious. A new study has shed light on the role of the centriolar protein centrin-2: reducing levels of centrin-2 in HeLa cells has been found to block centriole duplication, eventually leading to cell death.     

Is proteolysis dependent on phosphorus in fresh water?

Abstract HPA proteolytic assay was used to study the dependence of proteolysis on phosphorus in fresh water. Inorganic phosphate (P_i) stimulated the growth of bacteria producing proteases in water when P was limiting factor, but did not affect the biochemical activity of enzymes which were P-in-dependent. In proteolytic assays, bacteria utilised nitrogen and carbon from HPA. Therefore, during long incubations, significant increases in microbial biomass were observed. The original HPA procedure [12] gives artificial and non-realistic values of proteolytic rates in aquatic habitats due to accelerated and uncontrolled bacterial growth and enzyme production during the assay. The use of toluene to prevent microbial growth in HPA assays is recommended [10].     

Protein S-nitrosylation: What's going on in plants?

Nitric oxide (NO) is now recognized as a key regulator of plant physiological processes. Understanding the mechanisms by which NO exerts its biological functions has been the subject of extensive research. Several components of the signaling pathways relaying NO effects in plants, including second messengers, protein kinases, phytohormones, and target genes, have been characterized. In addition, there is now compelling experimental evidence that NO partly operates through posttranslational modification of proteins, notably via S-nitrosylation and tyrosine nitration. Recently, proteome-wide scale analyses led to the identification of numerous protein candidates for S-nitrosylation in plants. Subsequent biochemical and in silico structural studies revealed certain mechanisms through which S-nitrosylation impacts their functions. Furthermore, first insights into the physiological relevance of S-nitrosylation, particularly in controlling plant immune responses, have been recently reported. Collectively, these discoveries greatly extend our knowledge of NO functions and of the molecular processes inherent to signal transduction in plants.     

Who is publishing in Theriogenology and on what subjects?

An analysis of 503 articles published in the journal Theriogenology in 1984, 1987 and 1990 was conducted to identify research trends and researchers publishing in the journal. A 30.5% increase in the number of papers published was found for 1990. During the 3yr period studied, the United States and Canada accounted for 63.1% of the total number of articles published, followed by European countries with 14.3%, and by Asia with 12.0%. At least 1 paper was published from 41 countries. The United States, at the top of the list, increased its share from 16% in 1984 to 21% in 1990. The number of papers from Japan increased significantly while the percentage of participation from Europe declined. The female animal was the sole subject of 63.2% of the articles, and cattle were the most researched species, appearing in 44.3% of the studies. Although the estrous cycle was the most studied reproductive event in all 3 yr, there was also a trend for the popularity of this topic to decrease in favor of the subject fertilization. The number of authors per paper increased significantly over the years analyzed, as did the number of studies carried out in international cooperation. Institutes of higher education were represented in almost 70% of the papers, followed by research institutes (12.8%). The present analysis confirms the central role that the journal Theriogenology plays in the world-wide communication of research results in animal reproduction.     

E-cadherin downregulation in cancer: fuel on the fire?

The development, maintenance and repair of tissue requires an exquisite balance between cell proliferation, cell adhesion and cell motility. Equally, tumour initiation and progression are characterized by not only the abnormal expression of genes involved in cell proliferation and survival but also by genes responsible for the control of cell adhesion and cell motility. Central to the process of cell-cell adhesion in epithelial tissues is E-cadherin. Loss of E-cadherin function in tumours results in the rapid progression of relatively benign adenomas to invasive, metastatic carcinomas. Germline mutation of the E-cadherin gene predisposes to diffuse, poorly differentiated gastric cancer, and its downregulation in sporadic tumours is associated with poor clinical prognosis.     

Benefits in Cash or in Kind? A Community Consultation on Types of Benefits in Health Research on the Kenyan Coast

BackgroundProviding benefits and payments to participants in health research, either in cash or in kind, is a common but ethically controversial practice. While much literature has concentrated on appropriate levels of benefits or payments, this paper focuses on less well explored ethical issues around the nature of study benefits, drawing on views of community members living close to an international health research centre in Kenya.MethodsThe consultation, including 90 residents purposively chosen to reflect diversity, used a two-stage deliberative process. Five half-day workshops were each followed by between two and four small group discussions, within a two week period (total 16 groups). During workshops and small groups, facilitators used participatory methods to share information, and promote reflection and debate on ethical issues around types of benefits, including cash, goods, medical and community benefits. Data from workshop and field notes, and voice recordings of small group discussions, were managed using Nvivo 10 and analysed using a Framework Analysis approach.

Findings and Conclusions

The methods generated in-depth discussion with high levels of engagement. Particularly for the most-poor, under-compensation of time in research carries risks of serious harm. Cash payments may best support compensation of costs experienced; while highly valued, goods and medical benefits may be more appropriate as an ‘appreciation’ or incentive for participation. Community benefits were seen as important in supporting but not replacing individual-level benefits, and in building trust in researcher-community relations. Cash payments were seen to have higher risks of undue inducement, commercialising relationships and generating family conflicts than other benefits, particularly where payments are high. Researchers should consider and account for burdens families may experience when children are involved in research. Careful context-specific research planning and skilled and consistent communication about study benefits and payments are important, including in mitigating potential negative effects.     

Is There Selection on RFLP Differences in Mitochondrial Dna?

Experimental populations of Drosophila simulans were established for the purpose of detecting the presence or absence of selection on a restriction fragment length polymorphism in mitochondrial DNA (mtDNA). It was then discovered that the founding strains differed with respect to the Rickettsia-mediated incompatibility system in this species, which is maternally transmitted together with the mtDNA differences. A population model was constructed using the known fitness effects of the incompatibility system, with the result that the population trajectories can be completely explained by the effects of the microorganism with no need to invoke selection on mtDNA. The strong conclusion is that in this case we can rule out the strong selection proposed by MacRae and Anderson to explain the "dramatic mtDNA changes" in their Drosophila pseudoobscura populations. The population theory used for the experiments is discussed in the context of natural populations. Estimated parameters include the possibility that with two populations, one with the organism and one without it, there may be no bias as to which will invade the other, which in turn suggests no global tendency for the infection to spread or decline.     

Do neurons in the vertebrate CNS migrate on laminin?

In adult rat brain the extracellular matrix glycoprotein, laminin, is found only in basement membranes, but is transiently expressed by astrocytes after brain injury. Here, I show that laminin also appears in immature brain cells during CNS development, and that its presence coincides with phases of neuronal migration. In early embryos, laminin is seen throughout the whole thickness of the forming brain, and is apparently synthesized by the cells, as judged by its intracytoplasmic localization. As development proceeds, intracellular laminin becomes restricted to the periventricular regions while punctate deposits of laminin follow the course of vimentin-positive radial glial fibers. In most brain regions, the adult pattern of laminin expression is achieved by birth. In the post-natal rat cerebellum, however, laminin is detected in external granule cells, in Purkinje cells, and in punctate deposits along the radial Bergmann glial fibers. By day 24 after birth, when the migration of external granule cells is complete, all laminin immunoreactivity disappears from these structures. The transient expression of laminin in regions where neurons are migrating raises the possibility that laminin plays a role in neuronal migration during CNS development.     

OECD guidelines on open access: commercialization in disguise?

The Organisation for Economic Co-operation and Development (OECD) has published a new set of principles and guidelines to promote open access to datasets and results from publicly funded research. However, there is reason to think twice about the implications of making demands for transparency and open access for publicly funded research only. How will such demands affect incentives and research agendas? Might this new regulation of publicly funded research have undesirable effects on the quality and value of research? Placing the OECD guidelines in a broader context of research regulation, we argue that they might provide a further push toward collaboration with commercially sponsored research and reinforce incentive structures that favour the creation of commercial value.     

Middleborns Disadvantaged? Testing Birth-Order Effects on Fitness in Pre-Industrial Finns

Parental investment is a limited resource for which offspring compete in order to increase their own survival and reproductive success. However, parents might be selected to influence the outcome of sibling competition through differential investment. While evidence for this is widespread in egg-laying species, whether or not this may also be the case in viviparous species is more difficult to determine. We use pre-industrial Finns as our model system and an equal investment model as our null hypothesis, which predicts that (all else being equal) middleborns should be disadvantaged through competition. We found no overall evidence to suggest that middleborns in a family are disadvantaged in terms of their survival, age at first reproduction or lifetime reproductive success. However, when considering birth-order only among same-sexed siblings, first-, middle- and lastborn sons significantly differed in the number of offspring they were able to rear to adulthood, although there was no similar effect among females. Middleborn sons appeared to produce significantly less offspring than first- or lastborn sons, but they did not significantly differ from lastborn sons in the number of offspring reared to adulthood. Our results thus show that taking sex differences into account is important when modelling birth-order effects. We found clear evidence of firstborn sons being advantaged over other sons in the family, and over firstborn daughters. Therefore, our results suggest that parents invest differentially in their offspring in order to both preferentially favour particular offspring or reduce offspring inequalities arising from sibling competition.     

Better than fish on land? Hearing across metamorphosis in salamanders

Early tetrapods faced an auditory challenge from the impedance mismatch between air and tissue in the transition from aquatic to terrestrial lifestyles during the Early Carboniferous (350 Ma). Consequently, tetrapods may have been deaf to airborne sounds for up to 100 Myr until tympanic middle ears evolved during the Triassic. The middle ear morphology of recent urodeles is similar to that of early ‘lepospondyl’ microsaur tetrapods, and experimental studies on their hearing capabilities are therefore useful to understand the evolutionary and functional drivers behind the shift from aquatic to aerial hearing in early tetrapods. Here, we combine imaging techniques with neurophysiological measurements to resolve how the change from aquatic larvae to terrestrial adult affects the ear morphology and sensory capabilities of salamanders. We show that air-induced pressure detection enhances underwater hearing sensitivity of salamanders at frequencies above 120 Hz, and that both terrestrial adults and fully aquatic juvenile salamanders can detect airborne sound. Collectively, these findings suggest that early atympanic tetrapods may have been pre-equipped to aerial hearing and are able to hear airborne sound better than fish on land. When selected for, this rudimentary hearing could have led to the evolution of tympanic middle ears.     

Does personality in small rodents vary depending on population density?

Personality means an individual's unique way of behaving and reacting to the environment. It is a stable and heritable trait, which is expressed consistently in different situations. The aim of our study was to develop novel tests to depict the personality structure of the bank vole Myodes glareolus, and to determine if the phase of the population cycle, i.e. population density, affects personality. We focused on some central aspects of bank vole behaviour: mobility, risk taking, exploratory behaviour, dominance, and aggressive behaviour towards pups. These behaviours were chosen because they directly affect bank vole survival or fitness or are classified as important factors of personality in other species. In total, 192 males from different populations went through four behavioural tests, in which 20 variables were measured. The tests were repeated after 3 weeks, which verified that all traits were stable, i.e. repeatable between trials. Three personality compounds emerged, named extroversion, novelty seeking and infanticide. Extroversion included dominance and mobility, while novelty seeking consisted of risk taking and exploration. Infanticide encompassed all indices measuring harmful behaviour towards pups. Mobility and dominance were connected, possibly because both seem to depend on condition. Time spent in captivity increased extroversion, which may be explained by good food, stable conditions and acclimation to strong social cues. Novelty seeking was connected to repeatability which could mean that novelty avoiding individuals adjust their behaviour to match new environments. Population density affected the infanticide trait but not novelty seeking or extroversion.     

Neuroprotective Agents: Is Effective on Toxicity in Glial Cells?

1. Glial cells are the most abundant cell population in the central nervous system. The aim of this study was to examine the effects of melatonin, 7-nitroindazole, and riluzole on glutamate toxicity in primary glial cell culture. 2. Glutamate toxicity was induced by addition of 100 μM glutamate to the cultures, and then 100 μM melatonin, 500 μM 7-nitroindazole, and 10 (M riluzole were administered in different groups. Lactate Dehydrogenase activity and nitrite levels were determined at the 1st, 6th, and 24th h. 3. Melatonin, 7-nitroindazole, and riluzole decrease Lactate Dehydrogenase activity at the 1st, 6th, and 24th h (at all hours, p<0.05). Nitrite levels were decreased by melatonin and riluzole at the 1st, 6th, and 24th h. 4. In this study, we observed that melatonin, 7-nitroindazole, and riluzole are effective as protective agents on glutamate toxicity in mixed glial cells.     

Parental guidance? Trans-generational influences on offspring life history in mosquitoes

Parental effects are important factors that might influence evolutionary and ecological aspects of parasite vectors and the parasites they transmit. A recent study demonstrated the importance of parental rearing conditions on the malaria vector Anopheles stephensi. When parents are reared in a food-limited environment their offspring have increased bloodmeal sizes and larger clutches. The study highlights that ecological studies are vital for understanding vectors of disease and ultimately for developing effective control strategies.