Search

Abstract Low back pain (LBP) is a global issue involving biological, psychological, and social factors. Pain-related fear has been shown to influence movement behavior, however, its association with some measures of movement behavior, such as spinal movement variability, remains inconclusive. To further investigate this, spinal kinematics during various activities of daily living (i.e., walking, running, lifting, and stair climbing) of 49 patients with chronic LBP and a group of 51 sex-, age-, and BMI-matched healthy controls were used to calculate lumbar spine movement variability which was quantified using different indices (i.e., coefficient of variation, coupling angle variability in vector coding, deviation phase of the continuous relative phase and an angle-angular velocity variability). General and task-specific pain-related fear was assessed using the Tampa Scale of Kinesiophobia and the Photograph Series of Daily Activities—Short Electronic Version, respectively. Linear regression analyses showed no significant association between movement variability and pain-related fear, however, the sample consisted of younger individuals with moderate disability and with low levels of pain and pain-related fear. In addition, the different variability indices were weakly correlated and varied greatly depending on the method used and the task performed. Therefore, comparisons between studies with different movement variability calculation methods or different activities should be treated with caution.

Cortical reorganization and its potential pathological significance are being increasingly studied in musculoskeletal disorders such as chronic low back pain (CLBP) patients. However, detailed sensory-topographic maps of the human back are lacking, and a baseline characterization of such representations, reflecting the somatosensory organization of the healthy back, is needed before exploring potential sensory map reorganization. To this end, a novel pneumatic vibrotactile stimulation method was used to stimulate paraspinal sensory afferents, while studying their cortical representations in unprecedented detail. In 41 young healthy participants, vibrotactile stimulations at 20 Hz and 80 Hz were applied bilaterally at nine locations along the thoracolumbar axis while functional magnetic resonance imaging (fMRI) was performed. Model-based whole-brain searchlight representational similarity analysis (RSA) was used to investigate the organizational structure of brain activity patterns evoked by thoracolumbar sensory inputs. A model based on segmental distances best explained the similarity structure of brain activity patterns that were located in different areas of sensorimotor cortices, including the primary somatosensory and motor cortices and parts of the superior parietal cortex, suggesting that these brain areas process sensory input from the back in a “dermatomal” manner. The current findings provide a sound basis for testing the “cortical map reorganization theory” and its pathological relevance in CLBP.

Microtubules (MTs) are built from α-/β-tubulin dimers and used as tracks by kinesin and dynein motors to transport a variety of cargos, such as mRNAs, proteins, and organelles, within the cell. Tubulins are subjected to several post-translational modifications (PTMs). Glutamylation is one of them, and it is responsible for adding one or more glutamic acid residues as branched peptide chains to the C-terminal tails of both α- and β-tubulin. However, very little is known about the specific modifications found on the different tubulin isotypes in vivo and the role of these PTMs in MT transport and other cellular processes in vivo. In this study, we found that in Drosophila ovaries, glutamylation of α-tubulin isotypes occurred clearly on the C-terminal ends of αTub84B and αTub84D (αTub84B/D). In contrast, the ovarian α-tubulin, αTub67C, is not glutamylated. The C-terminal ends of αTub84B/D are glutamylated at several glutamyl sidechains in various combinations. Drosophila TTLL5 is required for the mono- and poly-glutamylation of ovarian αTub84B/D and with this for the proper localization of glutamylated microtubules. Similarly, the normal distribution of kinesin-1 in the germline relies on TTLL5. Next, two kinesin-1-dependent processes, the precise localization of Staufen and the fast, bidirectional ooplasmic streaming, depend on TTLL5, too, suggesting a causative pathway. In the nervous system, a mutation of TTLL5 that inactivates its enzymatic activity decreases the pausing of anterograde axonal transport of mitochondria. Our results demonstrate in vivo roles of TTLL5 in differential glutamylation of α-tubulins and point to the in vivo importance of α-tubulin glutamylation for cellular functions involving microtubule transport.

Direct writing methods are a generic and simple means to produce designed structures in three dimensions (3D). The printing is achieved by extruding printing materials through a nozzle, which provides a platform to deliver a wide range of materials. Although this method has been routinely used for 3D printing at macroscopic scales, miniaturization to micrometer and nanometer scales and building hierarchical structures at multidimensional scales represent new challenges in research and development. The current work addresses these challenges by combining the spatial precision of atomic force microscopy (AFM) and local delivery capability of microfluidics. Specialized AFM probes serve dual roles of a microscopy tip and a delivery tool, enabling the miniaturization of 3D printing via direct material delivery. Stacking grids of 20 μm periodicity were printed layer-by-layer covering 1 mm × 1 mm regions. The spatial fidelity was measured to be several nanometers, which is among the highest in 3D printing. The results clearly demonstrate the feasibility of achieving high precision 3D nanoprinting with nanometer feature size and accuracy with practical throughput and overall size. This work paves the way for advanced applications of 3D hierarchical nanostructures.

Direct writing methods are a generic and simple means to produce designed structures in three dimensions (3D). The printing is achieved by extruding printing materials through a nozzle, which provides a platform to deliver a wide range of materials. Although this method has been routinely used for 3D printing at macroscopic scales, miniaturization to micrometer and nanometer scales and building hierarchical structures at multidimensional scales represent new challenges in research and development. The current work addresses these challenges by combining the spatial precision of atomic force microscopy (AFM) and local delivery capability of microfluidics. Specialized AFM probes serve dual roles of a microscopy tip and a delivery tool, enabling the miniaturization of 3D printing via direct material delivery. Stacking grids of 20 μm periodicity were printed layer-by-layer covering 1 mm × 1 mm regions. The spatial fidelity was measured to be several nanometers, which is among the highest in 3D printing. The results clearly demonstrate the feasibility of achieving high precision 3D nanoprinting with nanometer feature size and accuracy with practical throughput and overall size. This work paves the way for advanced applications of 3D hierarchical nanostructures.

Many proteins exist in various proteoforms but detecting these variants by bottom-up proteomics remains difficult. Here, the authors present a computational approach based on peptide correlation analysis to identify and characterize proteoforms from bottom-up proteomics data.

Small ruminant lentiviruses (SRLVs), i.e., CAEV and MVV, cause insidious infections with life-long persistence and a slowly progressive disease, impairing both animal welfare and productivity in affected herds. The complex diagnosis of SRLVs currently combines serological methods including whole-virus and peptide-based ELISAs and Immunoblot. To improve the current diagnostic protocol, we analyzed 290 sera of animals originating from different European countries in parallel with three commercial screening ELISAs, Immunoblot as a confirmatory assay and five SU5 peptide ELISAs for genotype differentiation. A newly developed nested real-time PCR was carried out for the detection and genotype differentiation of the virus. Using a heat-map display of the combined results, the drawbacks of the current techniques were graphically visualized and quantified. The immunoblot and the SU5-ELISAs exhibited either unsatisfactory sensitivity or insufficient reliability in the differentiation of the causative viral genotype, respectively. The new truth standard was the concordance of the results of two out of three screening ELISAs and the PCR results for serologically false negative samples along with genotype differentiation. Whole-virus antigen-based ELISA showed the highest sensitivity (92.2%) and specificity (98.9%) among the screening tests, whereas PCR exhibited a sensitivity of 75%.

Hypertension and diabetes mellitus are highly correlated, but the underlying mechanisms are only partly understood. Therefore, the aim of our study was to investigate the relationships between plasma levels of glucagon-like peptide-1, a key factor in the regulation of glucose homeostasis, and various blood pressure indices. Healthy adults aged 25 to 41 years were enrolled in a population-based study. Established cardiovascular disease, diabetes mellitus, or a body mass index >35 kg/m² were exclusion criteria. Fasting plasma glucagon-like peptide-1 levels as determined with a novel high-sensitive assay and ambulatory blood pressure data were available in 1479 participants not using antihypertensive treatment. Median age of our population was 38 years. Mean systolic and diastolic blood pressure across increasing glucagon-like peptide-1 quartiles were 120.6, 122.8, 123.2, and 124.9 mm Hg and 77.1, 78.7, 78.9, and 79.9 mm Hg, respectively. We found a linear relationship of glucagon-like peptide-1 with 24-hour ambulatory blood pressure after multivariable adjustment (β per 1 log-unit increase 2.01; 95% confidence interval, 1.02-3.00; P<0.0001 for systolic and 1.22; 0.47-1.97; P=0.002 for diastolic blood pressure). In separate analyses, glucagon-like peptide-1 was significantly related to both awake (β per 1 log-unit increase 2.05; 1.02-3.09; P=0.0001 for systolic and 1.15; 0.35-1.96; P=0.005 for diastolic blood pressure) and asleep blood pressure (β per 1 log-unit increase 1.34; 0.26-2.42; P=0.01 for systolic and 1.05; 0.26-1.84; P=0.009 for diastolic blood pressure). In conclusion, plasma levels of glucagon-like peptide-1 are significantly associated with both systolic and diastolic blood pressure levels. [ABSTRACT FROM AUTHOR]

Differences in the way human and mouse fibroblasts experience senescence in culture had long puzzled researchers. While senescence of human cells is mediated by telomere shortening, Parrinello et al. demonstrated that senescence of mouse cells is caused by extreme oxygen sensitivity. It was hypothesized that the striking difference in oxygen sensitivity between mouse and human cells explains their different rates of aging. To test if this hypothesis is broadly applicable, we cultured cells from 16 rodent species with diverse lifespans in 3% and 21% oxygen and compared their growth rates. Unexpectedly, fibroblasts derived from laboratory mouse strains were the only cells demonstrating extreme sensitivity to oxygen. Cells from hamster, muskrat, woodchuck, capybara, blind mole rat, paca, squirrel, beaver, naked mole rat and wild-caught mice were mildly sensitive to oxygen, while cells from rat, gerbil, deer mouse, chipmunk, guinea pig and chinchilla showed no difference in the growth rate between 3% and 21% oxygen. We conclude that, although the growth of primary fibroblasts is generally improved by maintaining cells in 3% oxygen, the extreme oxygen sensitivity is a peculiarity of laboratory mouse strains, possibly related to their very long telomeres, and fibroblast oxygen sensitivity does not directly correlate with species' lifespan.

The eukaryotic phylum Apicomplexa encompasses thousands of obligate intracellular parasites of humans and animals with immense socio-economic and health impacts. We sequenced nuclear genomes of Chromera velia and Vitrella brassicaformis, free-living non-parasitic photosynthetic algae closely related to apicomplexans. Proteins from key metabolic pathways and from the endomembrane trafficking systems associated with a free-living lifestyle have been progressively and non-randomly lost during adaptation to parasitism. The free-living ancestor contained a broad repertoire of genes many of which were repurposed for parasitic processes, such as extracellular proteins, components of a motility apparatus, and DNA- and RNA-binding protein families. Based on transcriptome analyses across 36 environmental conditions, Chromera orthologs of apicomplexan invasion-related motility genes were co-regulated with genes encoding the flagellar apparatus, supporting the functional contribution of flagella to the evolution of invasion machinery. This study provides insights into how obligate parasites with diverse life strategies arose from a once free-living phototrophic marine alga. DOI: http://dx.doi.org/10.7554/eLife.06974.001

Copyright of Antike Kunst is the property of Vereinigung der Freunde Antiker Kunst and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Antike Kunst is the property of Vereinigung der Freunde Antiker Kunst and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)