Loss of slc39a14 causes simultaneous manganese hypersensitivity and deficiency in zebrafish

Manganese neurotoxicity is a hallmark of Hypermanganesemia with Dystonia 2, an inherited manganese transporter defect caused by mutations in SLC39A14. To identify novel potential targets of manganese neurotoxicity we performed transcriptome analysis of slc39a14-/- mutant zebrafish unexposed and exposed to MnCl2. Differentially expressed genes mapped to the central nervous system and eye, and pathway analysis suggested that calcium dyshomeostasis and activation of the unfolded protein response are key features of manganese neurotoxicity. Consistent with this interpretation, MnCl2 exposure led to decreased whole animal calcium levels, locomotor defects and changes in neuronal activity within the telencephalon and optic tectum. In accordance with reduced tectal activity, slc39a14-/- zebrafish showed changes in visual phototransduction gene expression, absence of visual background adaptation and a diminished optokinetic reflex. Finally, numerous differentially expressed genes in mutant larvae normalised upon MnCl2 treatment indicating that, in addition to neurotoxicity, manganese deficiency is present either subcellularly or in specific cells or tissues. Overall, we assembled a comprehensive set of genes that mediate manganese-systemic responses and found a highly correlated and modulated network associated with calcium dyshomeostasis and cellular stress

Progress in Classical and Quantum Variational Principles

We review the development and practical uses of a generalized Maupertuis least action principle in classical mechanics, in which the action is varied under the constraint of fixed mean energy for the trial trajectory. The original Maupertuis (Euler-Lagrange) principle constrains the energy at every point along the trajectory. The generalized Maupertuis principle is equivalent to Hamilton's principle. Reciprocal principles are also derived for both the generalized Maupertuis and the Hamilton principles. The Reciprocal Maupertuis Principle is the classical limit of Schr\"{o}dinger's variational principle of wave mechanics, and is also very useful to solve practical problems in both classical and semiclassical mechanics, in complete analogy with the quantum Rayleigh-Ritz method. Classical, semiclassical and quantum variational calculations are carried out for a number of systems, and the results are compared. Pedagogical as well as research problems are used as examples, which include nonconservative as well as relativistic systems

Simulation of heat transport in low-dimensional oscillator lattices

The study of heat transport in low-dimensional oscillator lattices presents a formidable challenge. Theoretical efforts have been made trying to reveal the underlying mechanism of diversified heat transport behaviors. In lack of a unified rigorous treatment, approximate theories often may embody controversial predictions. It is therefore of ultimate importance that one can rely on numerical simulations in the investigation of heat transfer processes in low-dimensional lattices. The simulation of heat transport using the non-equilibrium heat bath method and the Green-Kubo method will be introduced. It is found that one-dimensional (1D), two-dimensional (2D) and three-dimensional (3D) momentum-conserving nonlinear lattices display power-law divergent, logarithmic divergent and constant thermal conductivities, respectively. Next, a novel diffusion method is also introduced. The heat diffusion theory connects the energy diffusion and heat conduction in a straightforward manner. This enables one to use the diffusion method to investigate the objective of heat transport. In addition, it contains fundamental information about the heat transport process which cannot readily be gathered otherwise.Comment: Article published in: Thermal transport in low dimensions: From statistical physics to nanoscale heat transfer, S. Lepri, ed. Lecture Notes in Physics, vol. 921, pp. 239 - 274, Springer-Verlag, Berlin, Heidelberg, New York (2016

Mechanochemical Cu( ii ) complexes and propargylamine synthetic adventures †

We synthesized and characterized known and new Cu(ii)–salen complexes and investigated their efficacy in yielding propargylamines (PAs) via an A3 coupling reaction mechanochemically. Although the method appears simple, we explicitly describe synthetic obstacles that urge unavoidable solvent use to isolate the molecular entities in high purity. The recovered complexes retain structure and catalytic efficacy, and a library of twenty-four known and unknown PAs are isolated in very good to excellent yields. The scope and limitations of this method are presented

Computational prediction of pressure change in the vicinity of tidal stream turbines and the consequences for fish survival rate

The presence of Tidal Stream Turbines (TST) for tidal power production, leads to changes in the local physical environment that could affect fish. While other work has considered the implications with respect to conventional hydroelectric devices (i.e. hydroelectric dams), including studies such as physical impact with the rotors and pressure variation effects, this research considers the effects of sudden changes in pressure and turbulence on the hypothetical fish with respect to TSTs. Computational fluid dynamics (CFD) is used to investigate changes to the environment, and thus study the implications for fish. Two CFD methods are employed, an embedded Blade Element representation of the rotor in a RANS CFD model, and a blade resolved geometry using a moving reference frame. A new data interpretation approach is proposed as the primary source of environmental impact data; ‘rate of change of pressure’ with time along a streamtrace. This work also presents results for pressure, pressure gradients, shear rates and turbulence to draw conclusions about changes to the local physical environment. The assessment of the local impact is discussed in terms of the implications to individual fish passing a single or array of TST devices

Mutations in SLC39A14 disrupt manganese homeostasis and cause childhood-onset parkinsonism-dystonia

Although manganese is an essential trace metal, little is known about its transport and homeostatic regulation. Here we have identified a cohort of patients with a novel autosomal recessive manganese transporter defect caused by mutations in SLC39A14. Excessive accumulation of manganese in these patients results in rapidly progressive childhood-onset parkinsonism-dystonia with distinctive brain magnetic resonance imaging appearances and neurodegenerative features on post-mortem examination. We show that mutations in SLC39A14 impair manganese transport in vitro and lead to manganese dyshomeostasis and altered locomotor activity in zebrafish with CRISPR-induced slc39a14 null mutations. Chelation with disodium calcium edetate lowers blood manganese levels in patients and can lead to striking clinical improvement. Our results demonstrate that SLC39A14 functions as a pivotal manganese transporter in vertebrates

Mutations in SLC39A14 disrupt manganese homeostasis and cause childhood-onset parkinsonism-dystonia.

Although manganese is an essential trace metal, little is known about its transport and homeostatic regulation. Here we have identified a cohort of patients with a novel autosomal recessive manganese transporter defect caused by mutations in SLC39A14. Excessive accumulation of manganese in these patients results in rapidly progressive childhood-onset parkinsonism-dystonia with distinctive brain magnetic resonance imaging appearances and neurodegenerative features on post-mortem examination. We show that mutations in SLC39A14 impair manganese transport in vitro and lead to manganese dyshomeostasis and altered locomotor activity in zebrafish with CRISPR-induced slc39a14 null mutations. Chelation with disodium calcium edetate lowers blood manganese levels in patients and can lead to striking clinical improvement. Our results demonstrate that SLC39A14 functions as a pivotal manganese transporter in vertebrates.Action Medical ResearchThis is the final version of the article. It first appeared from Nature Publishing Group via http://dx.doi.org/10.1038/ncomms1160

Recovery of a US Endangered Fish

BACKGROUND: More fish have been afforded US Endangered Species Act protection than any other vertebrate taxonomic group, and none has been designated as recovered. Shortnose sturgeon (Acipenser brevirostrum) occupy large rivers and estuaries along the Atlantic coast of North America, and the species has been protected by the US Endangered Species Act since its enactment. METHODOLOGY/PRINCIPAL FINDINGS: Data on the shortnose sturgeon in the Hudson River (New York to Albany, NY, USA) were obtained from a 1970s population study, a population and fish distribution study we conducted in the late 1990s, and a fish monitoring program during the 1980s and 1990s. Population estimates indicate a late 1990s abundance of about 60,000 fish, dominated by adults. The Hudson River population has increased by more than 400% since the 1970s, appears healthy, and has attributes typical for a long-lived species. Our population estimates exceed the government and scientific population recovery criteria by more than 500%, we found a positive trend in population abundance, and key habitats have remained intact despite heavy human river use. CONCLUSIONS/SIGNIFICANCE: Scientists and legislators have called for changes in the US Endangered Species Act, the Act is being debated in the US Congress, and the Act has been characterized as failing to recover species. Recovery of the Hudson River population of shortnose sturgeon suggests the combination of species and habitat protection with patience can yield successful species recovery, even near one of the world's largest human population centers