Parkinson's disease (PD) presently is conceptualized as a protein aggregation disease in which pathology involves both the enteric and the central nervous system, possibly spreading from one to ...another via the vagus nerves. As gastrointestinal dysfunction often precedes or parallels motor symptoms, the enteric system with its vast diversity of microorganisms may be involved in PD pathogenesis. Alterations in the enteric microbial taxonomic level of L-DOPA-naïve PD patients might also serve as a biomarker.
We performed metagenomic shotgun analyses and compared the fecal microbiomes of 31 early stage, L-DOPA-naïve PD patients to 28 age-matched controls.
We found increased Verrucomicrobiaceae (Akkermansia muciniphila) and unclassified Firmicutes, whereas Prevotellaceae (Prevotella copri) and Erysipelotrichaceae (Eubacterium biforme) were markedly lowered in PD samples. The observed differences could reliably separate PD from control with a ROC-AUC of 0.84. Functional analyses of the metagenomes revealed differences in microbiota metabolism in PD involving the ẞ-glucuronate and tryptophan metabolism. While the abundances of prophages and plasmids did not differ between PD and controls, total virus abundance was decreased in PD participants. Based on our analyses, the intake of either a MAO inhibitor, amantadine, or a dopamine agonist (which in summary relates to 90% of PD patients) had no overall influence on taxa abundance or microbial functions.
Our data revealed differences of colonic microbiota and of microbiota metabolism between PD patients and controls at an unprecedented detail not achievable through 16S sequencing. The findings point to a yet unappreciated aspect of PD, possibly involving the intestinal barrier function and immune function in PD patients. The influence of the parkinsonian medication should be further investigated in the future in larger cohorts.
Introduction
Tether breakage is a frequent mechanical complications after vertebral body tethering (VBT), but not all patients with a breakage show loss of correction. The reason of this clinical ...finding has not yet been clarified. We hypothesized that the integrity of the tether is relevant only in the early stages after VBT, when it drives growth modulation and tissue remodelling. After these mechanisms have taken place, the tether loses its function and a breakage will not alter the new shape of the spine. Thus, tether breakage would have a greater clinical relevance when occurring shortly after surgery.
Methods
All consecutive patients who underwent VBT and had a min. 2-year follow-up were included. The difference in curve magnitude between the 1st standing x-ray and the last follow-up was calculated (ΔCobb). For each curve, the presence and timing of tether breakage were recorded. The curves were grouped according to if and when the breakage was observed (no breakage, breakage at 0–6 months, 6–12 months, > 12 months). The ΔCobb was compared among these groups with the analysis of variance (ANOVA).
Results
Data from 152 curves were available: 68 with no breakage, 12 with a breakage at 0–6 months, 37 at 6–12 months and 35 > 12 months. The ANOVA found significant difference in the ΔCobb among the groups (Sum of square 2553.59; degree of freedom 3; mean of square 851.1; Fisher test 13.8;
P
< 0.0001). Patients with no breakage or breakage at > 12 months had similar ΔCobb (mean 4.8° and 7.8°, respectively,
P
= 0.3), smaller than the 0–6 or 6–12 groups (15.8° and 13.8°, respectively).
Conclusion
Tether breakage leads to a consistent loss of correction when occurring within the first 12 months, while it has limited clinical relevance when occurring later on.
Triacylglycerol (TAG) is the main storage lipid in plants. Acyl-CoA: diacylglycerol acyltransferase (DGAT1 and DGAT2) and phospholipid: diacylglycerol acyltransferase (PDAT) can catalyze TAG ...synthesis. It is unclear how these three independent genes are regulated in developing seeds, and particularly if they have specific functions in the high accumulation of unusual fatty acids in seed oil. The expression patterns of DGAT1, DGAT2 and a PDAT in relation to the accumulation of oil and epoxy and hydroxy fatty acids in developing seeds of the plant species Vernonia galamensis, Euphorbia lagascae, Stokesia laevis and castor that accumulate high levels of these fatty acids in comparison with soybean and Arabidopsis were investigated. The expression patterns of DGAT1, DGAT2 and the PDAT are consistent with all three enzymes playing a role in the high epoxy or hydroxy fatty acid accumulation in developing seeds of these plants. PDAT and DGAT2 transcript levels are present at much higher levels in developing seeds of epoxy and hydroxy fatty acid accumulating plants than in soybeans or Arabidopsis. Moreover, PDAT, DGAT1 and DGAT2 are found to be expressed in many different plant tissues, suggesting that these enzymes may have other roles in addition to seed oil accumulation. DGAT1 appears to be a major enzyme for seed oil accumulation at least in Arabidopsis and soybeans. For the epoxy and hydroxy fatty acid accumulating plants, DGAT2 and PDAT also show expression patterns consistent with a role in the selective accumulation of these unusual fatty acids in seed oil.
Palmitoleate (cis-Δ9-16:1) shows numerous health benefits such as increased cell membrane fluidity, reduced inflammation, protection of the cardiovascular system, and inhibition of oncogenesis. Plant ...oils containing this unusual fatty acid can also be sustainable feedstocks for producing industrially important and high-demand 1-octene. Vegetable oils rich in palmitoleate are the ideal candidates for biodiesel production. Several wild plants are known that can synthesize high levels of palmitoleate in seeds. However, low yields and poor agronomic characteristics of these plants limit their commercialization. Metabolic engineering has been developed to create oilseed crops that accumulate high levels of palmitoleate or other unusual fatty acids, and significant advances have been made recently in this field, particularly using the model plant Arabidopsis as the host. The engineered targets for enhancing palmitoleate synthesis include overexpression of Δ9 desaturase from mammals, yeast, fungi, and plants, down-regulating KASII, coexpression of an ACP-Δ9 desaturase in plastids and CoA-Δ9 desaturase in endoplasmic reticulum (ER), and optimizing the metabolic flux into triacylglycerols (TAGs). This review will mainly describe the recent progress towards producing palmitoleate in transgenic plants by metabolic engineering along with our current understanding of palmitoleate biosynthesis and its regulation, as well as highlighting the bottlenecks that require additional investigation by combining lipidomics, transgenics and other “-omics” tools. A brief review of reported health benefits and non-food uses of palmitoleate will also be covered.
In this work, the role of jasmonic acid (JA) in leaf senescence is examined. Exogenous application of JA caused premature senescence in attached and detached leaves in wild-type Arabidopsis but ...failed to induce precocious senescence of JA-insensitive mutant coi1 plants, suggesting that the JA-signaling pathway is required for JA to promote leaf senescence. JA levels in senescing leaves are 4-fold higher than in non-senescing ones. Concurrent with the increase in JA level in senescing leaves, genes encoding the enzymes that catalyze most of the reactions of the JA biosynthetic pathway are differentially activated during leaf senescence in Arabidopsis, except for allene oxide synthase, which is constitutively and highly expressed throughout leaf development. Arabidopsis lipoxygenase 1 (cytoplasmic) expression is greatly increased but lipoxygenase 2 (plastidial) expression is sharply reduced during leaf senescence. Similarly, AOC1 (allene oxide cyclase 1), AOC2, and AOC3 are all up-regulated, whereas AOC4 is down-regulated with the progression of leaf senescence. The transcript levels of 12-oxo-PDA reductase 1 and 12-oxo-PDA reductase 3 also increase in senescing leaves, as does PED1 (encoding a 3-keto-acyl-thiolase for β-oxidation). This represents the first report, to our knowledge, of an increase in JA levels and expression of oxylipin genes during leaf senescence, and indicates that JA may play a role in the senescence program.
The third part of our work on variational inelasticity with long-range effects outlines a formulation and finite element implementation of micromechanically-motivated multiplicative gradient ...plasticity for single crystals. In order to partially overcome the complexity of full multislip scenarios, we suggest a new viscous regularized formulation of rate-independent crystal plasticity, that exploits in a systematic manner the long- and short-range nature of the involved variables. To this end, we outline a multifield scenario, where the macro-deformation and the plastic slips on crystallographic systems are the primary fields. Related to these primary fields, we define as the long-range state the deformation gradient, the plastic slips and their gradients. We then introduce as the short-range plastic state the plastic deformation map, the dislocation density tensor and scalar hardening parameters associated with the slip systems. It is then shown that the evolution of the short range state is fully determined by the evolution of the long-range state. This separation into long- and short-range states is systematically exploited in the algorithmic treatment by a new update structure, where the short-range variables play the role of a local history base. The model problem under consideration accounts in a canonical format for basic effects related to statistically stored and geometrically necessary dislocation flow, yielding micro-force balances including non-convex cross-hardening, kinematic hardening and size effects. Further key ingredients of the proposed algorithmic formulation are geometrically exact updates of the short-range state and a distinct regularization of the rate-independent dissipation function that preserves the range of the elastic domain. The formulation is shown to be fully variational in nature, governed by rate-type continuous and incremental algorithmic variational principles. We demonstrate the modeling capabilities and algorithmic performance by means of representative numerical examples for multislip scenarios in fcc single crystals.
The extraordinary properties of shape-memory alloys stem from the formation and evolution of their complex microstructure. At lower temperatures, this microstructure typically consists of martensitic ...laminates with coherent twin boundaries. We suggest a variational-based phase field model at finite strains for the formation and dissipative evolution of such two-variant martensitic twinned laminate microstructures. The starting point is a geometric discussion of the link between sharp interface topologies and their regularisation, which is connected to the notion of Γ-convergence. To model the energy storage in the two-phase laminates, we propose an interface energy that is coherence-dependent and a bulk energy that vanishes in the interface region, thus allowing for a clear separation of the two contributions. The dissipation related to phase transformation is modelled by use of a dissipation potential that leads to a Ginzburg-Landau type evolution equation for the phase field. We construct distinct rate-type continuous and finite-step-sized incremental variational principles for the proposed dissipative material and demonstrate its modelling capabilities by means of finite element simulations of laminate formation and evolution in martensitic CuAlNi.
Background noise in metagenomic studies is often of high importance and its removal requires extensive post-analytic, bioinformatics filtering. This is relevant as significant signals may be lost due ...to a low signal-to-noise ratio. The presence of plasmid residues, that are frequently present in reagents as contaminants, has not been investigated so far, but may pose a substantial bias. Here we show that plasmid sequences from different sources are omnipresent in molecular biology reagents. Using a metagenomic approach, we identified the presence of the (pol) of equine infectious anemia virus in human samples and traced it back to the expression plasmid used for generation of a commercial reverse transcriptase. We found fragments of multiple other expression plasmids in human samples as well as commercial polymerase preparations. Plasmid contamination sources included production chain of molecular biology reagents as well as contamination of reagents from environment or human handling of samples and reagents. Retrospective analyses of published metagenomic studies revealed an inaccurate signal-to-noise differentiation. Hence, the plasmid sequences that seem to be omnipresent in molecular biology reagents may misguide conclusions derived from genomic/metagenomics datasets and thus also clinical interpretations. Critical appraisal of metagenomic data sets for the possibility of plasmid background noise is required to identify reliable and significant signals.
Purpose
Short stems for total hip arthroplasty are an alternative to traditional conventional long stems. Short stems are designed to facilitate minimal-invasive surgery, improve bone-stock ...preservation, and mimic a physiological load distribution. However, there is little evidence of the long-term outcome of short stems. This study aims to analyze the ten year survival rates and clinical outcome of one specific metaphyseal short hip stem implant.
Methods
We retrospectively analyzed the patient records of the patients who underwent a total hip arthroplasty with a monoblock partial collum sparing metaphyseal short hip stem prosthesis in 2008 and 2009 in our clinic. Patients were contacted, and clinical follow-up was recorded using the German version of the modified Harris Hip Score. Furthermore, complications, revision surgery, and post-operative radiographs were analyzed.
Results
Data from 339 primary implantations in 322 patients were retrieved. The mean follow-up was 10.6 years. Seven patients underwent a revision. The ten year survival rate with any revision surgery as the endpoint was 97.5%. The mean modified Harris Hip Score was 86 points (range 30 to 91 points). Five patients had an intraoperative fracture of the femur (1.6%). Two patients (0.6%) had a dislocation of the hip. The stem tip-to-cortex distance, measured in the anterior posterior view, was 2.6 mm (range 0 to 8.3 mm).
Conclusion
The ten year survival rate of our used monoblock partial collum sparing metaphyseal short hip stem implant is comparable to traditional stems for total hip arthroplasty.
Vernolic acid (cis-12-epoxy-octadeca-cis-9-enoic acid) is valuable as a renewable chemical feedstock. This fatty acid can accumulate to high levels in the seed oil of some plant species such as ...Vernonia galamensis and Stokesia laevis which are unsuitable for large-scale production. A cost-effective alternative for production of epoxy fatty acids is to genetically engineer its biosynthesis in commercial oilseeds. An epoxygenase cDNA (SlEPX) responsible for vernolic acid synthesis and two acyl-CoA : diacylglycerol acyltransferase cDNAs (VgDGAT1 and VgDGAT2) catalysing triacylglycerol (TAG) formation were cloned from developing seeds of S. laevis and V. galamensis. Co-expression of SlEPX and VgDGAT1 or VgDGAT2 greatly increases accumulation of vernolic acid both in petunia leaves and soybean somatic embryos. Seed-specific expression of VgDGAT1 and VgDGAT2 in SlEPX mature soybean seeds results in vernolic acid levels of ~15% and 26%. Both DGAT1 and DGAT2 increase epoxy fatty acid accumulation with DGAT2 having much greater impact.
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