Mitochondrial recoupling: a novel therapeutic strategy for cancer?

Recent findings link metabolic transformation of cancer cells to aberrant functions of mitochondrial uncoupling proteins (UCPs). By inducing proton leak, UCPs interfere with mitochondrial synthesis of adenosine 5′-triphosphate, which is also a key determinant of glycolytic pathways. In addition, UCP suppress the generation of superoxide, a byproduct of mitochondrial electron transport and a major source of oxidative stress. The near ubiquitous UCP2 becomes highly abundant in some cancers and may advance metabolic reprogramming, further disrupt tumour suppression, and promote chemoresistance. Here we review current evidence to suggest that inhibition of mitochondrial uncoupling may eliminate these responses and reveal novel anti-cancer strategies

Serbia and the Balkans: An Overview of Regional Cooperation

The paper gives an overview of Serbia’s participation in various forms of regional cooperation in the Balkans. This cooperation became especially important in the post-Dayton period. In the case of Serbia, it was pushed back by the Yugoslav war, which led to international sanctions and the 1999 military intervention by NATO. Therefore, Serbia’s full-fledged participation in regional organisations resumed only after the regime change of October 2000. European and Euro-Atlantic orientation constitutes today the principal direction of Serbia’s foreign policy and in this connection the developing regional cooperation in the Balkans, especially in their western part, is a prerequisite for Serbia’s future accession to the EU, which can become possible between 2014 and 2017. Serbia occupies a central place in the Balkan region. Situated at the crossroads of Europe and the Middle East, it has experienced the influences of both eastern and western civilisations. Recently, regional cooperation has become a prerequisite for Serbia’s EU accession as an externally determined process with rigorous conditions and increasing expectations. Therefore, in the framework of the present article, an overview of Belgrade’s role in that cooperation will be given

Teaching deep learning causal effects improves predictive performance

Causal inference is a powerful statistical methodology for explanatory analysis and individualized treatment effect (ITE) estimation, a prominent causal inference task that has become a fundamental research problem. ITE estimation, when performed naively, tends to produce biased estimates. To obtain unbiased estimates, counterfactual information is needed, which is not directly observable from data. Based on mature domain knowledge, reliable traditional methods to estimate ITE exist. In recent years, neural networks have been widely used in clinical studies. Specifically, recurrent neural networks (RNN) have been applied to temporal Electronic Health Records (EHR) data analysis. However, RNNs are not guaranteed to automatically discover causal knowledge, correctly estimate counterfactual information, and thus correctly estimate the ITE. This lack of correct ITE estimates can hinder the performance of the model. In this work we study whether RNNs can be guided to correctly incorporate ITE-related knowledge and whether this improves predictive performance. Specifically, we first describe a Causal-Temporal Structure for temporal EHR data; then based on this structure, we estimate sequential ITE along the timeline, using sequential Propensity Score Matching (PSM); and finally, we propose a knowledge-guided neural network methodology to incorporate estimated ITE. We demonstrate on real-world and synthetic data (where the actual ITEs are known) that the proposed methodology can significantly improve the prediction performance of RNN.Comment: 9 pages, 8 figures, in the process of SDM 202

Shooter localization and weapon classification with soldier-wearable networked sensors

The paper presents a wireless sensor network-based mobile countersniper system. A sensor node consists of a helmetmounted microphone array, a COTS MICAz mote for internode communication and a custom sensorboard that implements the acoustic detection and Time of Arrival (ToA) estimation algorithms on an FPGA. A 3-axis compass provides self orientation and Bluetooth is used for communication with the soldier’s PDA running the data fusion and the user interface. The heterogeneous sensor fusion algorithm can work with data from a single sensor or it can fuse ToA or Angle of Arrival (AoA) observations of muzzle blasts and ballistic shockwaves from multiple sensors. The system estimates the trajectory, the range, the caliber and the weapon type. The paper presents the system design and the results from an independent evaluation at the US Army Aberdeen Test Center. The system performance is characterized by 1-degree trajectory precision and over 95 % caliber estimation accuracy for all shots, and close to 100 % weapon estimation accuracy for 4 out of 6 guns tested

Experimental Demonstration of a Rowland Spectrometer for Spin Waves

We experimentally demonstrate the operation of a spin-wave Rowland spectrometer. In the proposed device geometry, spin waves are coherently excited on a diffraction grating and form an interference pattern that spatially separates spectral components of the incoming signal. The diffraction grating was created by focused-ion-beam irradiation, which was found to locally eliminate the ferrimagnetic properties of YIG, without removing the material. We found that in our experiments spin waves were created by an indirect mechanism, by exploiting nonlinear resonance between the grating and the coplanar waveguide. Our work paves the way for complex spin-wave optic devices -- chips that replicate the functionality of integrated optical devices on a chip-scale.Comment: 7 pages, 5 figures, presented at Joint European Magnetic Symposia (JEMS) 202

Correction: Impaired cellular bioenergetics caused by GBA1 depletion sensitizes neurons to calcium overload

n/

Fast, ultrasensitive detection of reactive oxygen species using a carbon nanotube based-electrocatalytic intracellular sensor

Herein, we report a highly sensitive electrocatalytic sensor-cell construct that can electrochemically communicate with the internal environment of immune cells (e.g., macrophages) via the selective monitoring of a particular reactive oxygen species (ROS), hydrogen peroxide. The sensor, which is based on vertically aligned single-walled carbon nanotubes functionalized with an osmium electrocatalyst, enabled the unprecedented detection of a local intracellular “pulse” of ROS on a short second time scale in response to bacterial endotoxin (lipopolysaccharide-LPS) stimulation. Our studies have shown that this initial pulse of ROS is dependent on NADPH oxidase (NOX) and toll like receptor 4 (TLR4). The results suggest that bacteria can induce a rapid intracellular pulse of ROS in macrophages that initiates the classical innate immune response of these cells to infection

Isolation of Oropouche Virus from Febrile Patient, Ecuador.

We report identification of an Oropouche virus strain in a febrile patient from Ecuador by using metagenomic sequencing and real-time reverse transcription PCR. Virus was isolated from patient serum by using Vero cells. Phylogenetic analysis of the whole-genome sequence showed the virus to be similar to a strain from Peru

DJ-1 is a redox sensitive adapter protein for high molecular weight complexes involved in regulation of catecholamine homeostasis

DJ-1 is an oxidation sensitive protein encoded by the PARK7 gene. Mutations in PARK7 are a rare cause of familial recessive Parkinson’s disease (PD), but growing evidence suggests involvement of DJ-1 in idiopathic PD. The key clinical features of PD, rigidity and bradykinesia, result from neurotransmitter imbalance, particularly the catecholamines dopamine (DA) and noradrenaline. We report in human brain and human SH-SY5Y neuroblastoma cell lines that DJ-1 predominantly forms high molecular weight (HMW) complexes that included RNA metabolism proteins hnRNPA1 and PABP1 and the glycolysis enzyme GAPDH. In cell culture models the oxidation status of DJ-1 determined the specific complex composition. RNA sequencing indicated that oxidative changes to DJ-1 were concomitant with changes in mRNA transcripts mainly involved in catecholamine metabolism. Importantly, loss of DJ-1 function upon knock down (KD) or expression of the PD associated form L166P resulted in the absence of HMW DJ-1 complexes. In the KD model, the absence of DJ-1 complexes was accompanied by impairment in catecholamine homeostasis, with significant increases in intracellular DA and noraderenaline levels. These changes in catecholamines could be rescued by re-expression of DJ-1. This catecholamine imbalance may contribute to the particular vulnerability of dopaminergic and noradrenergic neurons to neurodegeneration in PARK7-related PD. Notably, oxidised DJ-1 was significantly decreased in idiopathic PD brain, suggesting altered complex function may also play a role in the more common sporadic form of the disease