How Does a Single Cell Know When the Liver Has Reached Its Correct Size?

The liver is a multi-functional organ that regulates major physiological processes and that possesses a remarkable regeneration capacity. After loss of functional liver mass the liver grows back to its original, individual size through hepatocyte proliferation and apoptosis. How does a single hepatocyte ‘know’ when the organ has grown to its final size? This work considers the initial growth phase of liver regeneration after partial hepatectomy in which the mass is restored. There are strong and valid arguments that the trigger of proliferation after partial hepatectomy is mediated through the portal blood flow. It remains unclear, if either or both the concentration of metabolites in the blood or the shear stress are crucial to hepatocyte proliferation and liver size control. A cell-based mathematical model is developed that helps discriminate the effects of these two potential triggers. Analysis of the mathematical model shows that a metabolic load and a hemodynamical hypothesis imply different feedback mechanisms at the cellular scale. The predictions of the developed mathematical model are compared to experimental data in rats. The assumption that hepatocytes are able to buffer the metabolic load leads to a robustness against short-term fluctuations of the trigger which can not be achieved with a purely hemodynamical trigger.     

Human GAPDH Is a Target of Aspirin’s Primary Metabolite Salicylic Acid and Its Derivatives

The plant hormone salicylic acid (SA) controls several physiological processes and is a key regulator of multiple levels of plant immunity. To decipher the mechanisms through which SA’s multiple physiological effects are mediated, particularly in immunity, two high-throughput screens were developed to identify SA-binding proteins (SABPs). Glyceraldehyde 3-Phosphate Dehydrogenase (GAPDH) from plants (Arabidopsis thaliana) was identified in these screens. Similar screens and subsequent analyses using SA analogs, in conjunction with either a photoaffinity labeling technique or surface plasmon resonance-based technology, established that human GAPDH (HsGAPDH) also binds SA. In addition to its central role in glycolysis, HsGAPDH participates in several pathological processes, including viral replication and neuronal cell death. The anti-Parkinson’s drug deprenyl has been shown to suppress nuclear translocation of HsGAPDH, an early step in cell death and the resulting cell death induced by the DNA alkylating agent N-methyl-N’-nitro-N-nitrosoguanidine. Here, we demonstrate that SA, which is the primary metabolite of aspirin (acetyl SA) and is likely responsible for many of its pharmacological effects, also suppresses nuclear translocation of HsGAPDH and cell death. Analysis of two synthetic SA derivatives and two classes of compounds from the Chinese medicinal herb Glycyrrhiza foetida (licorice), glycyrrhizin and the SA-derivatives amorfrutins, revealed that they not only appear to bind HsGAPDH more tightly than SA, but also exhibit a greater ability to suppress translocation of HsGAPDH to the nucleus and cell death.     

Testing the Role of Climate Change in Species Decline: Is the Eastern Quoll a Victim of a Change in the Weather?

To conserve a declining species we first need to diagnose the causes of decline. This is one of the most challenging tasks faced by conservation practitioners. In this study, we used temporally explicit species distribution models (SDMs) to test whether shifting weather can explain the recent decline of a marsupial carnivore, the eastern quoll (Dasyurus viverrinus). We developed an SDM using weather variables matched to occurrence records of the eastern quoll over the last 60 years, and used the model to reconstruct variation through time in the distribution of climatically suitable range for the species. The weather model produced a meaningful prediction of the known distribution of the species. Abundance of quolls, indexed by transect counts, was positively related to the modelled area of suitable habitat between 1990 and 2004. In particular, a sharp decline in abundance from 2001 to 2003 coincided with a sustained period of unsuitable weather over much of the species’ distribution. Since 2004, abundance has not recovered despite a return to suitable weather conditions, and abundance and area of suitable habitat have been uncorrelated. We suggest that fluctuations in weather account for the species’ recent decline, but other unrelated factors have suppressed recovery.     

Examining the Interaction of Acceptance and Understanding: How Does the Relationship Change with a Focus on Macroevolution?

The goal of this research was to illuminate the relationship between students’ acceptance and understanding of macroevolution. Our research questions were: (1) Is there a relationship between knowledge of macroevolution and acceptance of the theory of evolution?; (2) Is there a relationship between the amount of college level biology course work and acceptance of evolutionary theory and knowledge of macroevolution?; and (3) Can college student acceptance of the theory of evolution and knowledge of macroevolution change over the course of a semester? The research participants included 667 students from a first-semester biology course and 74 students from the evolutionary biology course. Data were collected using both the MATE (a measure of the acceptance of evolutionary theory) and the MUM (a measure of understanding of macroevolution). Pre-instruction data were obtained for the introductory biology course, and pre- and post-data were obtained for the evolutionary biology course. Analysis revealed acceptance of evolution (as measured by the MATE) was correlated to understanding of macroevolution, and the number of biology courses was significantly correlated to acceptance and knowledge of macroevolution. Finally, there was a statistically significant change in students’ understanding of macroevolution and acceptance of evolution after the one-semester evolutionary biology course. Significance of these findings is discussed.     

Is the Drug-Responsive NADH Oxidase of the Cancer Cell Plasma Membrane a Molecular Target for Adriamycin?

Enhanced growth inhibition and antitumor responses to adriamycin have been observed repeatedly from several laboratories using impermeant forms of adriamycin where entry into the cell was greatly reduced or prevented. Our laboratory has described an NADH oxidase activity at the external surface of plasma membrane vesicles from tumor cells where inhibition by an antitumor sulfonylurea, N-(4-methylphenylsulfonyl)-N-(4-chlorophenyl)urea (LY181984), and by the vanilloid, capsaicin (8-methyl-N-vanillyl-6-noneamide) correlated with inhibition of growth. Here we report that the oxidation of NADH by isolated plasma membrane vesicles was inhibited, as well, by adriamycin. An external site of inhibition was indicated from studies where impermeant adriamycin conjugates were used. The EC₅₀ for inhibition of the oxidase of rat hepatoma plasma membranes by adriamycin was several orders of magnitude less than that for rat liver. Adriamycin cross-linked to diferric transferrin and other impermeant supports also was effective in inhibition of NADH oxidation by isolated plasma membrane vesicles and in inhibition of growth of cultured cells. The findings suggest the NADH oxidase of the plasma membrane as a growth-related adriamycin target at the surface of cancer cells responsive to adriamycin. Whereas DNA intercalation remains clearly one of the principal bases for the cytotoxic action of free adriamycin, this second site, possibly related to a more specific antitumor action, may be helpful in understanding the enhanced efficacy reported previously for immobilized adriamycin forms compared to free adriamycin.     

Is Shape of a Fresh and Dried Leaf the Same?

Plants kept as dried herbarium specimens share many characteristics with their living counterparts, but there are some substantial differences between them. Due to dehydration, leaves of herbarium specimens change not only their mass and colour, but in many cases change their dimensions, too. The present study aimed to determine whether leaf shape changes during the drying process. A total of 794 pairs of fresh and dried leaves or leaflets of 22 plant taxa were studied. The shape of the blades was quantified using elliptic Fourier analysis combined with principal component analysis. In addition, area and mass of the leaves were measured. Statistical tests were applied for comparing fresh and dried leaves. The results indicate that the preservation process of pressing and drying plants for herbarium purposes causes changes in leaf shape. In general, the shape changes were directional. As the shape of fresh and dried plants is different, it is strongly recommended that shape analyses should be performed on datasets containing either of the leaf types.     

Is the Cell Membrane a Universal Rate-Limiting Barrier to the Movement of Water between the Living Cell and Its Surrounding Medium?

With the use of a newly introduced technique, the "influx profile analysis," we studied the diffusion of tritiated water in and out of frog ovarian eggs at 25°C. The results show that the rate-limiting step in the exchange of labeled water is not permeation through the cell membrane but diffusion in the bulk of the intracellular water.     

Consequences of Cathodal Stimulation for Behavior: When Does It Help and When Does It Hurt Performance?

Cathodal Transcranial Direct Current Stimulation (C-tDCS) has been reported, across different studies, to facilitate or hinder performance, or simply to have no tangible effect on behavior. This discrepancy is most prominent when C-tDCS is used to alter a cognitive function, questioning the assumption that cathodal stimulation always compromises performance. In this study, we aimed to study the effect of two variables on performance in a simple cognitive task (letter Flanker), when C-tDCS was applied to the left prefrontal cortex (PFC): (1) the time of testing relative to stimulation (during or after), and (2) the nature of the cognitive activity during stimulation in case of post-tDCS testing. In three experiments, we had participants either perform the Flanker task during C-tDCS (Experiment 1), or after C-tDCS. When the Flanker task was administered after C-tDCS, we varied whether during stimulation subjects were engaged in activities that posed low (Experiment 2) or high (Experiment 3) demands on the PFC. Our findings show that the nature of the task during C-tDCS has a systematic influence on the outcome, while timing per se does not.     

Is the originality of a species measurable?

In this paper, we introduce the concept of 'originality of a species within a set' in order to indicate the average rarity of all the features belonging to this species. Using a phylogenetic tree of 70 species of New World terrestrial Carnivora, we suggest measuring the originality by a probability distribution. This maximizes the expected number of features shared by two species randomly drawn from the set. By using this new index, we take account of branch lengths whereas current indices of originality focus on tree topology. As a supplement to Nee and May's optimizing algorithm, we find that originality must be one of the criteria used in conservation planning.     

When does a functional correctly describe both the structure and the energy of the transition state?

Requiring that several properties are well reproduced is a severe test on density functional approximations. This can be assessed through the estimation of joint and conditional success probabilities. An example is provided for a small set of molecules, for properties characterizing the transition states (geometries and energies).     

Does Forest Continuity Enhance the Resilience of Trees to Environmental Change?

There is ample evidence that continuously existing forests and afforestations on previously agricultural land differ with regard to ecosystem functions and services such as carbon sequestration, nutrient cycling and biodiversity. However, no studies have so far been conducted on possible long-term (>100 years) impacts on tree growth caused by differences in the ecological continuity of forest stands. In the present study we analysed the variation in tree-ring width of sessile oak (Quercus petraea (Matt.) Liebl.) trees (mean age 115–136 years) due to different land-use histories (continuously existing forests, afforestations both on arable land and on heathland). We also analysed the relation of growth patterns to soil nutrient stores and to climatic parameters (temperature, precipitation). Tree rings formed between 1896 and 2005 were widest in trees afforested on arable land. This can be attributed to higher nitrogen and phosphorous availability and indicates that former fertilisation may continue to affect the nutritional status of forest soils for more than one century after those activities have ceased. Moreover, these trees responded more strongly to environmental changes – as shown by a higher mean sensitivity of the tree-ring widths – than trees of continuously existing forests. However, the impact of climatic parameters on the variability in tree-ring width was generally small, but trees on former arable land showed the highest susceptibility to annually changing climatic conditions. We assume that incompletely developed humus horizons as well as differences in the edaphon are responsible for the more sensitive response of oak trees of recent forests (former arable land and former heathland) to variation in environmental conditions. We conclude that forests characterised by a long ecological continuity may be better adapted to global change than recent forest ecosystems.     

When Is Exposure to a Natural Disaster Traumatic? Comparison of a Trauma Questionnaire and Disaster Exposure Inventory

Few studies have compared the sensitivity of trauma questionnaires to disaster inventories for assessing the prevalence of exposure to natural disaster or associated risk for post-disaster psychopathology. The objective of this analysis was to compare reporting of disaster exposure on a trauma questionnaire (Brief Trauma Questionnaire [BTQ]) to an inventory of disaster experience. Between 2011 and 2014, a sample of 841 reproductive-aged southern Louisiana women were interviewed using the BTQ and completed a detailed inventory about exposure to hurricanes and flooding. Post-traumatic stress disorder (PTSD) symptomology was measured with the Post-Traumatic Stress Checklist, and depression with the Edinburgh Depression Scale. The single question addressing disaster exposure on the BTQ had a sensitivity of between 65% and 70% relative to the more detailed questions. Reporting disaster exposure on the BTQ was more likely for those who reported illness/injury due to a hurricane or flood (74%-77%) or danger (77-79%), compared to those who reported damage (69-71%) or evacuation (64-68%). Reporting disaster exposure on the BTQ was associated with depression (odds ratio [OR] 2.29, 95% confidence interval [CI] 1.43-3.68). A single question is unlikely to be useful for assessing the degree of exposure to disaster across a broad population, and varies in utility depending on the mental health outcome of interest: the single trauma question is useful for assessing depression risk.