Footprint analysis of gait using a pressure sensor system.

The purpose of this study was to investigate if the detailed pressure data of the footprints of normal gait add essential information to the spatio-temporal variables of gait. The gait of 62 healthy adult subjects was investigated using GAITRite pressure sensor system. Each footprint was divided into 12 equal trapezoids and after that the hindfoot, midfoot and forefoot analysis was developed. A typical activation pattern of the sensors with two peaks of active area and peak pressure distribution during normal walking was obtained. The first peak reflected the heel strike, and the second peak reflected push-off at the end of the stance phase. The lowest pressure values were in the midfoot, where the lateral part of the foot activated sensors more than the medial part. The footprint patterns of right and left legs were symmetrical and corresponded with the symmetry found in the spatio-temporal variables of gait. The variability for the active area and the peak pressure were more pronounced for the lateral part of the midfoot and a smaller variation was seen in areas with concentrated observations (e.g. 1st, 2nd and 5th lateral trapezoids). Increasing active area in the forefoot was associated with decreasing pressure sensor activity in the midfoot. The footprint patterns identified the symmetry between the legs and at the same time revealed the velocity performance.     

On some recent insights in Integral Biomathics

This paper summarizes the results in Integral Biomathics obtained to this moment and provides an outlook for future research in the field.     

Economic transition and household food consumption: A study of Bulgaria from 1985 to 2002

Major economic transitions typically entail changes in the availability of and purchasing power for different types of foods leading to long-term changes in the composition of the diet. Bulgaria, a former Eastern Bloc country, underwent a difficult and protracted transition from a centralized to market economy with acute economic crises and a much slower recovery of income levels than in Poland, the Czech Republic, and Hungary. Using annual data from the Bulgarian National Household Survey, we study changes in the reported consumption of major foods (excluding alcoholic drinks) and their constituent macronutrients from 1985 to 2002, examining also the differences in dietary patterns between the period prior to and following the transition. The consumption of most major food items decreased, resulting in a fall in per capita energy consumption of 429 kcal/day (1.80 MJ/d), following the economic transition of 1991. As expected, the consumption of foods that were more expensive per unit of energy decreased greater than cheaper foods, -34% for animal products and -19% for visible fats, but only -10% for carbohydrates. These changes are related to the changes in income and market prices as well as the general negative trend in economic growth and hyperinflation in the mid-1990s. Thus, Bulgaria experienced a decrease in food consumption without significant changes in the dietary pattern following the economic transition of 1991. The fact that part of this decline may be attributed to continued economic challenges suggests that future transitions in the diet may be expected as economic development proceeds.     

Mapping of Heterogeneous Catalyst Degradation in Polymer Electrolyte Fuel Cells

Pt catalysts in polymer electrolyte fuel cells degrade heterogeneously as the catalyst particles are exposed to local variations throughout the catalyst layer during operation. State‐of‐the‐art analytical techniques for studying degradation of Pt catalysts do not possess fine spatial resolution to elucidate such non‐uniform degradation behavior at a large electrode level. A new methodology is developed to spatially resolve and quantify the heterogeneous Pt catalyst degradation over a large area (several cm²) of aged MEAs based on synchrotron X‐ray microdiffraction. PEFC single cells are aged using voltage cycling as an accelerated stress test and the degradation heterogeneity at a micrometer length scale is visualized by mapping Pt catalyst particle size after voltage cycling. It is demonstrated in detail that the Pt catalyst particle size growth is non‐uniform and follows the flow field geometry. The Pt particle size growth is greater in the area under the flow field land, while it is minimal in the area under the flow field channel. Additional non‐uniformity is observed with the Pt particle size increasing more rapidly at the air outlet area than the Pt particle size at the inlet area.     

NAR Breakthrough Article: Next-generation sequencing reveals the biological significance of the N2,3-ethenoguanine lesion in vivo

Etheno DNA adducts are a prevalent type of DNA damage caused by vinyl chloride (VC) exposure and oxidative stress. Etheno adducts are mutagenic and may contribute to the initiation of several pathologies; thus, elucidating the pathways by which they induce cellular transformation is critical. Although N²,3-ethenoguanine (N²,3-εG) is the most abundant etheno adduct, its biological consequences have not been well characterized in cells due to its labile glycosidic bond. Here, a stabilized 2′-fluoro-2′-deoxyribose analog of N²,3-εG was used to quantify directly its genotoxicity and mutagenicity. A multiplex method involving next-generation sequencing enabled a large-scale in vivo analysis, in which both N²,3-εG and its isomer 1,N²-ethenoguanine (1,N²-εG) were evaluated in various repair and replication backgrounds. We found that N²,3-εG potently induces G to A transitions, the same mutation previously observed in VC-associated tumors. By contrast, 1,N²-εG induces various substitutions and frameshifts. We also found that N²,3-εG is the only etheno lesion that cannot be repaired by AlkB, which partially explains its persistence. Both εG lesions are strong replication blocks and DinB, a translesion polymerase, facilitates the mutagenic bypass of both lesions. Collectively, our results indicate that N²,3-εG is a biologically important lesion and may have a functional role in VC-induced or inflammation-driven carcinogenesis.     

Genomic signatures of strain selection and enhancement in Bacillus atrophaeus var. globigii, a historical biowarfare simulant

Background

Despite the decades-long use of Bacillus atrophaeus var. globigii (BG) as a simulant for biological warfare (BW) agents, knowledge of its genome composition is limited. Furthermore, the ability to differentiate signatures of deliberate adaptation and selection from natural variation is lacking for most bacterial agents. We characterized a lineage of BGwith a long history of use as a simulant for BW operations, focusing on classical bacteriological markers, metabolic profiling and whole-genome shotgun sequencing (WGS).

Results

Archival strains and two “present day” type strains were compared to simulant strains on different laboratory media. Several of the samples produced multiple colony morphotypes that differed from that of an archival isolate. To trace the microevolutionary history of these isolates, we obtained WGS data for several archival and present-day strains and morphotypes. Bacillus-wide phylogenetic analysis identified B. subtilis as the nearest neighbor to B. atrophaeus. The genome of B. atrophaeus is, on average, 86% identical to B. subtilis on the nucleotide level. WGS of variants revealed that several strains were mixed but highly related populations and uncovered a progressive accumulation of mutations among the “military” isolates. Metabolic profiling and microscopic examination of bacterial cultures revealed enhanced growth of “military” isolates on lactate-containing media, and showed that the “military” strains exhibited a hypersporulating phenotype.

Conclusions

Our analysis revealed the genomic and phenotypic signatures of strain adaptation and deliberate selection for traits that were desirable in a simulant organism. Together, these results demonstrate the power of whole-genome and modern systems-level approaches to characterize microbial lineages to develop and validate forensic markers for strain discrimination and reveal signatures of deliberate adaptation.     

Identification versus counting protocols as sources of uncertainty in diatom-based ecological status assessments

The heterogeneity of oxygen distribution in a Hediste diversicolor burrow environment was investigated in a laboratory experiment using a 6-mm thick tank equipped with oxygen planar optodes. The two-dimensional oxygen distribution in a complete burrow was monitored every 2 min for 4 h. Oxygen concentrations fluctuated over a scale of minutes in the burrow lumen and wall (up to 2 mm) reflecting the balance between worm ventilation activity and oxygen consumption. The magnitude of the three surrounding micro-horizons (oxic, oscillating and anoxic) induced by the intermittent worm ventilation was spatially and temporally variable within the structure. Oxygen variations appeared to be controlled by distance from the sediment–water interface and the direction of water circulation. Moreover, there was an apparent ‘buffer effect’, induced by the proximity to the overlying water, which reduced the variations of lumen and wall oxygen in the upper part of the structure. These results highlight the heterogeneous distribution and dynamics of oxygen associated with H. diversicolor burrows and ventilation activity. They also highlight the necessity of integrating this complexity into the current burrow-base models in order to estimate the ecological importance of burrowing species in coastal ecosystems.     

Methylglyoxal modification of Nav1.8 facilitates nociceptive neuron firing and causes hyperalgesia in diabetic neuropathy

This study establishes a mechanism for metabolic hyperalgesia based on the glycolytic metabolite methylglyoxal. We found that concentrations of plasma methylglyoxal above 600 nM discriminate between diabetes-affected individuals with pain and those without pain. Methylglyoxal depolarizes sensory neurons and induces post-translational modifications of the voltage-gated sodium channel Na(v)1.8, which are associated with increased electrical excitability and facilitated firing of nociceptive neurons, whereas it promotes the slow inactivation of Na(v)1.7. In mice, treatment with methylglyoxal reduces nerve conduction velocity, facilitates neurosecretion of calcitonin gene-related peptide, increases cyclooxygenase-2 (COX-2) expression and evokes thermal and mechanical hyperalgesia. This hyperalgesia is reflected by increased blood flow in brain regions that are involved in pain processing. We also found similar changes in streptozotocin-induced and genetic mouse models of diabetes but not in Na(v)1.8 knockout (Scn10(-/-)) mice. Several strategies that include a methylglyoxal scavenger are effective in reducing methylglyoxal- and diabetes-induced hyperalgesia. This previously undescribed concept of metabolically driven hyperalgesia provides a new basis for the design of therapeutic interventions for painful diabetic neuropathy.