How can storage time and temperature affect enzymic activities in urines?

We measured a tubular brush-border enzyme (alanine aminopeptidase, AAP) and a lysosomal hydrolase (N-acetyl-beta-D-glucosaminidase, NAG) in morning urines from 15 healthy normal subjects to check if different storage times and temperatures could modify enzyme concentrations. Short-term (24 h) storage time at room temperature or 4 degrees C does not affect AAP and NAG activities. Both enzymes are well preserved at -70 degrees C. AAP dramatically falls after 1 month at -20 degrees C, lowering to about 8% of the initial value after only 4 days of storage. On the contrary, NAG is well preserved at these storage conditions. Centrifugation has revealed not critical for measurement of these two enzymes.     

Does fetal sex affect pregnancy outcome?

Background: In maternal fetal medicine, gender differences in outcome are often observed.Objective: This article reviews the fetal sex-dependent differences found in many aspects of pregnancy, from conception through birth.Methods: The MEDLINE, EMBASE, and Current Contents databases were searched, for the years 1985 to 2006, using the following Medical Subject Headings and text words: fetal gender, finale, female, sex ratio at birth, pregnancy outcome, preterm birth, and stillbirth. The search was not limited by language. In addition, the bibliographies of known relevant articles were examined to capture any reports not already identified in the electronic search. All reports that provided information on gender differences in pregnancy outcome were included for review.Results: An extremely high male-to-female ratio was found in fetuses born after very short-duration pregnancy; this level declined around the 20th week and stabilized at term. In the absence of manipulation, both the sex ratio at birth and the population sex ratio have been found to remain consistent. A higher incidence of preterm birth and premature preterm rupture of membranes has been observed in different populations among mothers of male newborns compared with mothers of females. It has been speculated that this higher incidence may be linked to the relatively greater weight at lower gestational age of male newborns versus females. Women carrying male fetuses had higher rates of gestational diabetes mellitus, fetal macrosomia, failure to progress during the first and second stages of labor, cord prolapse, nuchal cord, and true umbilical cord knots. Cesarean sections were also more frequently found among male neonates compared with females.Conclusions: Male sex is an independent risk factor for adverse pregnancy outcome. Evidence suggests that females have an advantage over males, with a better outcome in the perinatal period, particularly after preterm birth.Key words: fetal gender, male, female, sex ratio of birth, perinatal outcome.     

How do floating aquatic weeds affect wetland conservation and development? How can these effects be minimised?

The most important floating aquatic weeds (FAWs) are Eichhornia crassipes, Salvinia molesta and Pistia stratiotes. E. crassipes and P. stratiotes reproduce sexually. All three species reproduce asexually. E. crassipes and S. molesta have particularly high growth rates. All can form dense mats and growth rates are increased by high nutrient levels and temperatures. Spread between continents and watersheds is largely the result of human activities. Spread within watersheds is mostly via floating propagules. FAWs are known to affect water resource management, the continued existence of human riverine and wetland communities, and conservation of biodiversity. Waterways can be blocked, and the efficiency of irrigation and hydro generation impaired. People are affected by reduction of the fish catch, inability to travel by boat and consequent isolation from gardens, markets and health services, and also changes in populations of vectors of human and animal diseases. Biodiversity can be reduced and conservation value affected. It is proposed that rational application of physical, chemical and biological control of FAWs, and reduction of nutrient input should be part of every strategy for the sustainable management of wetlands.     

Why are women predisposed to autoimmune rheumatic diseases?

The majority of autoimmune diseases predominate in females. In searching for an explanation for this female excess, most attention has focused on hormonal changes - both exogenous changes (for example, oral contraceptive pill) and fluctuations in endogenous hormone levels particularly related to menstruation and pregnancy history. Other reasons include genetic differences, both direct (influence of genes on sex chromosomes) and indirect (such as microchimerism), as well as gender differences in lifestyle factors. These will all be reviewed, focusing on the major autoimmune connective tissue disorders: rheumatoid arthritis, systemic lupus erythematosus and scleroderma.     

Gene therapy for autoimmune diseases: quo vadis?

Biological therapies using antibodies and cytokines are becoming widespread for the treatment of chronic inflammatory autoimmune diseases. However, these treatments have several limitations - such as expense, the need for repeated injections and unwanted side-effects - that can be overcome by genetic delivery. This review summarizes the ingenuity, sophistication and variety of gene-therapy approaches that have been taken in the design of therapeutic molecules and vectors, the engineering of cells and the regulation of gene expression for the targeting of disease outcome. We focus our attention on multiple sclerosis, type 1 diabetes and rheumatoid arthritis.     

How statin drugs affect exosomes?

Statins reduce serum cholesterol and isoprenoids by the inhibition of cholesterol synthesis in the mevalonate pathway. Exosomes are extracellular vesicles (30–200 nm) released by all cells that regulate cell-to-cell communication in health and disease by transferring functional proteins, metabolites and nucleic acids to recipient cells. There are many reports that show an effect of statins on exosomes, from their production and release to their content and performance. In this review, we have summarized existing data on the impact of statins on the biosynthesis, secretion, content, uptake and function of exosomes.     

How noise in force fields can affect the structural refinement of protein models?

Structural refinement of predicted models of biological macromolecules using atomistic or coarse‐grained molecular force fields having various degree of error is investigated. The goal of this analysis is to estimate what is the probability for designing an effective structural refinement based on computations of conformational energies using force field, and starting from a structure predicted from the sequence (using template‐based or template‐free modeling), and refining it to bring the structure into closer proximity to the native state. It is widely believed that it should be possible to develop such a successful structure refinement algorithm by applying an iterative procedure with stochastic sampling and appropriate energy function, which assesses the quality (correctness) of protein decoys. Here, an analysis of noise in an artificially introduced scoring function is investigated for a model of an ideal sampling scheme, where the underlying distribution of RMSDs is assumed to be Gaussian. Sampling of the conformational space is performed by random generation of RMSD values. We demonstrate that whenever the random noise in a force field exceeds some level, it is impossible to obtain reliable structural refinement. The magnitude of the noise, above which a structural refinement, on average is impossible, depends strongly on the quality of sampling scheme and a size of the protein. Finally, possible strategies to overcome the intrinsic limitations in the force fields for impacting the development of successful refinement algorithms are discussed. Proteins 2012. © 2011 Wiley Periodicals, Inc.     

How weird can mimicry get?

Classical mimicry theory distinguishes clearly between the mutualistic resemblance between two or more defended species (muellerian mimicry), and the parasitic resemblance of a palatable species to a defended species (batesian mimicry). Modelling the behaviour of predators, without initially taking ecological complications into account, is a good strategy for exploring whether this division is valid. Two such behavioural models are described: conditioning theory, which simulates changes in motivational attack levels according to the norms of current learning theory; and saturation theory, which considers how a predator may become saturated with a particular toxic compound, and then cease feeding on the prey species that delivers it. This effect is to be clearly distinguished from simple satiation. Most formulations of the conditioning model allow the direction of reinforcement produced by a particular prey to change according the predator's current state of motivation: this leads to the existence of quasi-batesian mimicry, a parasitic mimicry between two species that could both be described as defended. At high densities, two prey species that share a chemical defense will be ‘muellerian mutualists’, mutually protecting each other against predators that have been saturated with the defensive compound. This mutualism may be accompanied by true muellerian mimicry of the colour patterns, or the patterns may be completely different. This can therefore be regarded as a form of mimicry in a non-visual communication channel. Even an apparently palatable prey species may be effectively unavailable to predators if its density is such as to deliver a particular nutrient in excess of the predator's need for a balanced diet. Such a nutrient in effect becomes a toxin, and such an abundant prey species would be partly defended and potentially able to act as the model in a mimicry system. Thus there might be protective mimicry between ‘palatable’ species, and a ‘palatable’ species might even function as the model for a ‘defended’ mimic. These unorthodox kinds of mimicry probably exist transiently during fluctuations of prey populations. It is less likely that these conditions persist for long enough to induce the evolution of mimicry, and the relationships perhaps usually occur when mimicry already exists for other reasons. Mimicry rings may be mutually stabilised by a combination of toxic mutualism and the exchange of species between the rings. Colour polymorphism in a defended species is strictly neutral whenever the population is dense enough to saturate the predator. This, as well as quasi-batesian mimicry, may help to explain the minority of warningly coloured species that are polymorphic. This revised version was published online in July 2006 with corrections to the Cover Date.     

How do synonymous mutations affect fitness?

While it has often been assumed that, in humans, synonymous mutations would have no effect on fitness, let alone cause disease, this position has been questioned over the last decade. There is now considerable evidence that such mutations can, for example, disrupt splicing and interfere with miRNA binding. Two recent publications suggest involvement of additional mechanisms: modification of protein abundance most probably mediated by alteration in mRNA stability and modification of protein structure and activity, probably mediated by induction of translational pausing. These case histories put a further nail into the coffin of the assumption that synonymous mutations must be neutral.     

How do cytokinins affect the cell?

The lecture presents modern knowledge of the mechanisms of cytokinin perception and signal transduction to the genes of primary and secondary responses. It also demonstrates the relations between the rapid cytokinin-induced processes and cytokinin-induced physiological effects. The characteristics of the cytokinin regulatory system and its role in the control of plant growth and development are discussed.     

How do toxicants affect epidemiological dynamics?

Populations are formed of their constituent interacting individuals, each with their own respective within‐host biological processes. Infection not only spreads within the host organism but also spreads between individuals. Here we propose and study a multilevel model which links the within‐host statuses of immunity and parasite density to population epidemiology under sublethal and lethal toxicant exposure. We analyse this nested model in order to better understand how toxicants impact the spread of disease within populations. We demonstrate that outbreak of infection within a population is completely determined by the level of toxicant exposure, and that it is maximised by intermediate toxicant dosage. We classify the population epidemiology into five phases of increasing toxicant exposure and calculate the conditions under which disease will spread, showing that there exists a threshold toxicant level under which epidemics will not occur. In general, higher toxicant load results in either extinction of the population or outbreak of infection. The within‐host statuses of the individual host also determine the outcome of the epidemic at the population level. We discuss applications of our model in the context of environmental epidemiology, predicting that increased exposure to toxicants could result in greater risk of epidemics within ecological systems. We predict that reducing sublethal toxicant exposure below our predicted safe threshold could contribute to controlling population level disease and infection.     

Mesenchymal stem cells in autoimmune diseases: hype or hope?

Intervention with mesenchymal stem cells (MSCs) represents a promising therapeutic tool in treatment-refractory autoimmune diseases. A new report by Schurgers and colleagues in a previous issue of Arthritis Research & Therapy sheds novel mechanistic insight into the pathways employed by MSCs to suppress T-cell proliferation in vitro, but, at the same time, indicates that MSCs do not influence T-cell reactivity and the disease course in an in vivo arthritis model. Such discrepancies between the in vitro and in vivo effects of potent cellular immune modulators should spark further research and should be interpreted as a sign of caution for the in vitro design of MSC-derived interventions in the setting of human autoimmune diseases.     

How do neurons die in neurodegenerative diseases?

Given that neurons are post-mitotic cells, their life span is generally long enough to reach that of humans. However, sometimes neurons die without recognizable causes, as a result of a process called neurodegeneration. Apart from when gene mutations can be correlated with disease, it is difficult to pinpoint molecules that are responsible for neuronal death. Therefore, neurons living in a 'sick state' for many years might reveal important information about neuronal death. Systematic and extensive single-neuron analysis of 'sick' neurons is expected to provide clues to the mechanisms of neurodegeneration. Moreover, the elimination of putative triggering and promoting factors involved in neurodegenerative disease might prevent disease progression.