Unnatural acts: The transition from Natural Principles to Laws of Nature in Early Modern science

This paper's aim is to explain the transition that occurred during the Early Modern period, from Principles of Nature to Laws of Nature. Natural Principles are taken to be innate to substances and arise from their natures, while Laws of Nature are external and imposed from without. The paper takes the view that to explain this transition, one needs to examine the history of philosophical theories of substantial action. It argues that during the late Middle Ages and in the Early Modern era, philosophers began to disentangle substantial actions from the nature of substances. This process of disentangling action eventually led to the concept of Laws of Nature, according to which laws compel a body to act in a certain way even though its nature does not.     

Year-round activity patterns in a hyperdiverse community of rainforest amphibians in Madagascar

Madagascar hosts a high diversity of amphibians estimated at over 500 species, nearly all of them endemic. Surprisingly few data are available on the activity cycles of this fauna, despite its importance for ecological, evolutionary and conservation research. Here we report the results of a year-round survey of amphibians along a transect bordering the Analamazaotra forest near Andasibe in central eastern Madagascar. During 120 transect walks evenly spaced through the year, a total of 2530 individuals of 40 species of anurans was observed. Abundance was higher during the warm/rainy season (December to April) and peaked in February. Of the five climatic predictors measured, only mean temperature and relative humidity showed high importance values, and multi-model averages indicate that these two variables have a strong effect on amphibian abundance along the transect. Species richness showed no evident peak during the study period and was best explained by a model including average temperature and rainfall. Canonical correspondence analysis indicates that Boophis sibilans, B. tephraeomystax, B. boehmei and Plethodontohyla notosticta were more frequently encountered along the transect on cold and humid days while Plethodontohyla mihanika, Gephyromantis boulengeri and Spinomantis aglavei were distinctly more abundant on cold and dry days, and Paradoxophyla palmata on warm and dry days. The results of our study flag a number of species as suitable candidates for future monitoring initiatives and suggest that a simple combination of visual and acoustic surveys can estimate amphibian activity with high sample sizes in Madagascar’s rainforests.     

Neurotrophin-conjugated nanoparticles prevent retina damage induced by oxidative stress

Glaucoma and other optic neuropathies are characterized by a loss of retinal ganglion cells (RGCs), a cell layer located in the posterior eye segment. Several preclinical studies demonstrate that neurotrophins (NTs) prevent RGC loss. However, NTs are rarely investigated in the clinic due to various issues, such as difficulties in reaching the retina, the very short half-life of NTs, and the need for multiple injections. We demonstrate that NTs can be conjugated to magnetic nanoparticles (MNPs), which act as smart drug carriers. This combines the advantages of the self-localization of the drug in the retina and drug protection from fast degradation. We tested the nerve growth factor and brain-derived neurotrophic factor by comparing the neuroprotection of free versus conjugated proteins in a model of RGC loss induced by oxidative stress. Histological data demonstrated that the conjugated proteins totally prevented RGC loss, in sharp contrast to the equivalent dose of free proteins, which had no effect. The overall data suggest that the nanoscale MNP-protein hybrid is an excellent tool in implementing ocular drug delivery strategies for neuroprotection and therapy.     

Haem oxygenase is synthetically lethal with the tumour suppressor fumarate hydratase

Fumarate hydratase (FH) is an enzyme of the tricarboxylic acid cycle (TCA cycle) that catalyses the hydration of fumarate into malate. Germline mutations of FH are responsible for hereditary leiomyomatosis and renal-cell cancer (HLRCC). It has previously been demonstrated that the absence of FH leads to the accumulation of fumarate, which activates hypoxia-inducible factors (HIFs) at normal oxygen tensions. However, so far no mechanism that explains the ability of cells to survive without a functional TCA cycle has been provided. Here we use newly characterized genetically modified kidney mouse cells in which Fh1 has been deleted, and apply a newly developed computer model of the metabolism of these cells to predict and experimentally validate a linear metabolic pathway beginning with glutamine uptake and ending with bilirubin excretion from Fh1-deficient cells. This pathway, which involves the biosynthesis and degradation of haem, enables Fh1-deficient cells to use the accumulated TCA cycle metabolites and permits partial mitochondrial NADH production. We predicted and confirmed that targeting this pathway would render Fh1-deficient cells non-viable, while sparing wild-type Fh1-containing cells. This work goes beyond identifying a metabolic pathway that is induced in Fh1-deficient cells to demonstrate that inhibition of haem oxygenation is synthetically lethal when combined with Fh1 deficiency, providing a new potential target for treating HLRCC patients.     

Leibniz and Newton on Space

This paper reexamines the historical debate between Leibniz and Newton on the nature of space. According to the traditional reading, Leibniz (in his correspondence with Clarke) produced metaphysical arguments (relying on the Principle of Sufficient Reason and the Principle of Identity of Indiscernibles) in favor of a relational account of space. Newton, according to the traditional account, refuted the metaphysical arguments with the help of an empirical argument based on the bucket experiment. The paper claims that Leibniz’s and Newton’s arguments cannot be understood apart from the distinct dialectics of their respective positions vis-à-vis Descartes’ theory of space and physics. Against the traditional reading, the paper argues that Leibniz and Newton are operating within a different metaphysics and different conceptions of “place,” and that their respective arguments can largely remain intact without undermining the other philosopher’s conception of space. The paper also takes up the task of clarifying the distinction between true and absolute motion, and of explaining the relativity of motion implied by Leibniz’s account. The paper finally argues that the two philosophers have different conceptions of the relation between metaphysics and science, and that Leibniz’s attempt to base physical theory on an underlying metaphysical account of forces renders his account of physics unstable.     

Biodegradable zinc-iron alloys: Complex study of corrosion behavior,mechanical properties and hemocompatibility

Zn-Fe alloys have been extensively investigated in this study with a view to their application as biodegradable bone implants. Biogenic element zinc is a very appropriate metal because of the ideal degradation rate compared to those of Mg and Fe. Studied alloys were made by compressing metallic powders in a content ratio of 100% Zn,Zn-1% Fe, Zn-2% Fe, Zn-5% Fe and Zn-10% Fe and sintering at 350°C for 1 h. Prepared samples were examined by optical microscopy, SEM and XRD. Corrosion behavior, mechanical testing and hemocompatibility were observed subsequently. The electrochemical performance of such materials was studied in the simulated body fluids. The enhanced corrosion rate was observed for all samples after iron addition due to the micro-galvanic effect between the pure Zn and Zn_(11)Fe intermetallic phase. The corrosion rate of the Zn-5% Fe alloyed sample was more than 20-times higher(2.89 mmpy) compared to the pure Zn. However, alloying with more than 5 wt %of iron diminished the mechanical performance of the material. Therefore, the performed mechanical and hemocompatibility tests showed acceptable biocompatibility of zinc and Zn-1% Fe and Zn-2% Fe samples.