Genomic variants in the FTO gene are associated with sporadic amyotrophic lateral sclerosis in Greek patients

Background: Amyotrophic lateral sclerosis (ALS) is a devastating disease whose complex pathology has been associated with a strong genetic component in the context of both familial and sporadic disease. Herein, we adopted a next-generation sequencing approach to Greek patients suffering from sporadic ALS (together with their healthy counterparts) in order to explore further the genetic basis of sporadic ALS (sALS). Results: Whole-genome sequencing analysis of Greek sALS patients revealed a positive association between FTO and TBC1D1 gene variants and sALS. Further, linkage disequilibrium analyses were suggestive of a specific diseaseassociated haplotype for FTO gene variants. Genotyping for these variants was performed in Greek, Sardinian, and Turkish sALS patients. A lack of association between FTO and TBC1D1 variants and sALS in patients of Sardinian and Turkish descent may suggest a founder effect in the Greek population. FTO was found to be highly expressed in motor neurons, while in silico analyses predicted an impact on FTO and TBC1D1 mRNA splicing for the genomic variants in question. Conclusions: To our knowledge, this is the first study to present a possible association between FTO gene variants and the genetic etiology of sALS. In addition, the next-generation sequencing-based genomics approach coupled with the two-step validation strategy described herein has the potential to be applied to other types of human complex genetic disorders in order to identify variants of clinical significance

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

New Keywords: Migration and Borders

“New Keywords: Migration and Borders” is a collaborative writing project aimed at developing a nexus of terms and concepts that fill-out the contemporary problematic of migration. It moves beyond traditional and critical migration studies by building on cultural studies and post-colonial analyses, and by drawing on a diverse set of longstanding author engagements with migrant movements. The paper is organized in four parts (i) Introduction, (ii) Migration, Knowledge, Politics, (iii) Bordering, and (iv) Migrant Space/Times. The keywords on which we focus are: Migration/Migration Studies; Militant Investigation; Counter-mapping; Border Spectacle; Border Regime; Politics of Protection; Externalization; Migrant Labour; Differential inclusion/exclusion; Migrant struggles; and Subjectivity

Nature-Inspired Optimization Algorithms for the 3D Reconstruction of Porous Media

One of the most challenging problems that are still open in the field of materials science is the 3D reconstruction of porous media using information from a single 2D thin image of the original material. Such a reconstruction is only feasible subject to some important assumptions that need to be made as far as the statistical properties of the material are concerned. In this study, the aforementioned problem is investigated as an explicitly formulated optimization problem, with the phase of each porous material point being decided such that the resulting 3D material model shows the same statistical properties as its corresponding 2D version. Based on this problem formulation, herein for the first time, several traditional (genetic algorithms—GAs, particle swarm optimization—PSO, differential evolution—DE), as well as recently proposed (firefly algorithm—FA, artificial bee colony—ABC, gravitational search algorithm—GSA) nature-inspired optimization algorithms were applied to solve the 3D reconstruction problem. These algorithms utilized a newly proposed data representation scheme that decreased the number of unknowns searched by the optimization process. The advantages of addressing the 3D reconstruction of porous media through the application of a parallel heuristic optimization algorithm were clearly defined, while appropriate experiments demonstrating the greater performance of the GA algorithm in almost all the cases by a factor between 5%–84% (porosity accuracy) and 3%–15% (auto-correlation function accuracy) over the PSO, DE, FA, ABC, and GSA algorithms were undertaken. Moreover, this study revealed that statistical functions of a high order need to be incorporated into the reconstruction procedure to increase the reconstruction accuracy

Novel Pathogenic Variants Leading to Sporadic Amyotrophic Lateral Sclerosis in Greek Patients

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive disease that affects motor neurons, leading to paralysis and death usually 3–5 years after the onset of symptoms. The investigation of both sporadic and familial ALS highlighted four main genes that contribute to the pathogenesis of the disease: SOD1, FUS, TARDBP and C9orf72. This study aims to provide a comprehensive investigation of genetic variants found in SOD1, FUS and TARDBP genes in Greek sporadic ALS (sALS) cases. Our sequencing analysis of the coding regions of the abovementioned genes that include the majority of the variants that lead to ALS in 32 sALS patients and 3 healthy relatives revealed 6 variants in SOD1, 19 variants in FUS and 37 variants in TARDBP, of which the SOD1 p.D90A and the FUS c.*356G&gt;A (rs886051940) variants have been previously associated with ALS, while two novel nonsense pathogenic variants were also identified, namely FUS p.R241* and TDP-43 p.Y214*. Our study contributes to the worldwide effort toward clarifying the genetic basis of sALS to better understand the disease’s molecular pathology.</p

Progress in the development of olfactory-based bioelectronic chemosensors.

Artificial chemosensory devices have a wide range of applications in industry, security, and medicine. The development of these devices has been inspired by the speed, sensitivity, and selectivity by which the olfactory system in animals can probe the chemical nature of the environment. In this review, we examine how molecular and cellular components of natural olfactory systems have been incorporated into artificial chemosensors, or bioelectronic sensors. We focus on the biological material that has been combined with signal transduction systems to develop artificial chemosensory devices. The strengths and limitations of different biological chemosensory material at the heart of these devices, as well as the reported overall effectiveness of the different bioelectronic sensor designs, is examined. This review also discusses future directions and challenges for continuing to advance development of bioelectronic sensors

Salt-Mediated Au-Cu Nanofoam and Au-Cu-Pd Porous Macrobeam Synthesis.

Multi-metallic and alloy nanomaterials enable a broad range of catalytic applications with high surface area and tuning reaction specificity through the variation of metal composition. The ability to synthesize these materials as three-dimensional nanostructures enables control of surface area, pore size and mass transfer properties, electronic conductivity, and ultimately device integration. Au-Cu nanomaterials offer tunable optical and catalytic properties at reduced material cost. The synthesis methods for Au-Cu nanostructures, especially three-dimensional materials, has been limited. Here, we present Au-Cu nanofoams and Au-Cu-Pd macrobeams synthesized from salt precursors. Salt precursors formed from the precipitation of square planar ions resulted in short- and long-range ordered crystals that, when reduced in solution, form nanofoams or macrobeams that can be dried or pressed into freestanding monoliths or films. Metal composition was determined with X-ray diffraction and energy dispersive X-ray spectroscopy. Nitrogen gas adsorption indicated an Au-Cu nanofoam specific surface area of 19.4 m²/g. Specific capacitance determined with electrochemical impedance spectroscopy was 46.0 F/g and 52.5 F/g for Au-Cu nanofoams and Au-Cu-Pd macrobeams, respectively. The use of salt precursors is envisioned as a synthesis route to numerous metal and multi-metallic nanostructures for catalytic, energy storage, and sensing applications

Colistin Methanesulfonate against Multidrug-Resistant Acinetobacter baumannii in an In Vitro Pharmacodynamic Model▿

Using an in vitro pharmacodynamic model, a multidrug-resistant strain of Acinetobacter baumannii was exposed to colistin methanesulfonate alone and in combination with ceftazidime. Pre- and postexposure colistin sulfate MICs were determined. A single daily dose of colistin methanesulfonate combined with continuous-infusion ceftazidime prevented regrowth and postexposure MIC increases