Background and purpose
Nerve tissue alterations have rarely been quantified in Charcot–Marie–Tooth type 1A (CMT1A) patients. The aim of the present study was to quantitatively assess the magnetic ...resonance imaging (MRI) anomalies of the sciatic and tibial nerves in CMT1A disease using quantitative neurography MRI. It was also intended to seek for correlations with clinical variables.
Methods
Quantitative neurography MRI was used in order to assess differences in nerve volume, proton density and magnetization transfer ratio in the lower limbs of CMT1A patients and healthy controls. Disease severity was evaluated using the Charcot–Marie–Tooth Neuropathy Score version 2, Charcot–Marie–Tooth examination scores and Overall Neuropathy Limitations Scale scores. Electrophysiological measurements were performed in order to assess the compound motor action potential and the Motor Unit Number Index. Clinical impairment was evaluated using muscle strength measurements and Charcot–Marie–Tooth examination scores.
Results
A total of 32 CMT1A patients were enrolled and compared to 13 healthy subjects. The 3D nerve volume, magnetization transfer ratio and proton density were significantly different in CMT1A patients for the whole sciatic and tibial nerve volume. The sciatic nerve volume was significantly correlated with the whole set of clinical scores whereas no correlation was found between the tibial nerve volume and the clinical scores.
Conclusion
Nerve injury could be quantified in vivo using quantitative neurography MRI and the corresponding biomarkers were correlated with clinical disability in CMT1A patients. The sensitivity of the selected metrics will have to be assessed through repeated measurements over time during longitudinal studies to evaluate structural nerve changes under treatment.
The concept of milk as a healthy food has opened the way for studies on milk components, from nutrients to microRNAs, molecules with broad regulatory properties present in large quantities in milk. ...Characterization of these components has been performed in several species, such as humans and bovine, depending on the stages of lactation. Here, we have studied the variation in milk microRNA composition according to genetic background. Using high throughput sequencing, we have characterized and compared the milk miRNomes of Holstein and Normande cattle, dairy breeds with distinct milk production features, in order to highlight microRNAs that are essential for regulation of the lactation process. In Holstein and Normande milk, 2,038 and 2,030 microRNAs were identified, respectively, with 1,771 common microRNAs, of which 1,049 were annotated and 722 were predicted. The comparison of the milk miRNomes of two breeds allowed to highlight 182 microRNAs displaying significant differences in the abundance. They are involved in the regulation of lipid metabolism and mammary morphogenesis and development, which affects lactation. Our results provide new insights into the regulation of molecular mechanisms involved in milk production.
Puerperal sepsis, a major cause of death of young women in Europe in the 1800s, was due predominantly to the gram-positive pathogen group A Streptococcus Studies conducted during past decades have ...shown that serotype M28 strains are the major group A Streptococcus organisms responsible for many of these infections. To begin to increase our understanding of their enrichment in puerperal sepsis, we sequenced the genome of a genetically representative strain. This strain has genes encoding a novel array of prophage virulence factors, cell-surface proteins, and other molecules likely to contribute to host-pathogen interactions. Importantly, genes for 7 inferred extracellular proteins are encoded by a 37.4-kb foreign DNA element that is shared with group B Streptococcus and is present in all serotype M28 strains. Proteins encoded by the 37.4-kb element were expressed extracellularly and in human infections. Acquisition of foreign genes has helped create a disease-specialist clone of this pathogen
It is well known that interstitials affect the mechanical properties of titanium and titanium alloys. Their effects on the fatigue properties of titanium foams have not, however, been documented in ...the literature. This paper presents the effect of the oxygen content on the static and dynamic compression properties of titanium foams. Increasing the oxygen content from 0.24 to 0.51 wt% O in solution significantly increases the yield strength and reduces the ductility of the foams. However, the fatigue limit is not significantly affected by the oxygen content and falls within the 92 MPa ± 12 MPa range for all specimens investigated in this study. During cyclic loading, deformation is initially coming from cumulative creep followed by the formation of microcracks. The coalescence of these microcracks is responsible for the rupture of the specimens. Fracture surfaces of the specimens having lower oxygen content show a more ductile aspect than the specimens having higher oxygen content.
On December 5, 2022, an indirect drive fusion implosion on the National Ignition Facility (NIF) achieved a target gain G_{target} of 1.5. This is the first laboratory demonstration of exceeding ..."scientific breakeven" (or G_{target}>1) where 2.05 MJ of 351 nm laser light produced 3.1 MJ of total fusion yield, a result which significantly exceeds the Lawson criterion for fusion ignition as reported in a previous NIF implosion H. Abu-Shawareb et al. (Indirect Drive ICF Collaboration), Phys. Rev. Lett. 129, 075001 (2022)PRLTAO0031-900710.1103/PhysRevLett.129.075001. This achievement is the culmination of more than five decades of research and gives proof that laboratory fusion, based on fundamental physics principles, is possible. This Letter reports on the target, laser, design, and experimental advancements that led to this result.
Summary Background Charcot–Marie–Tooth disease type 1A (CMT1A) is a hereditary peripheral neuropathy that affects roughly one in 5000 births. No specific therapy currently exists for this ...degenerative disorder, which is characterised by distal progressive muscle atrophy and sensory loss, although ascorbic acid has been shown to reduce demyelination and improve muscle function in a transgenic mouse model of CMT1A. We tested the safety and efficacy of ascorbic acid in adults with CMT1A. Methods This 12-month, randomised, double-blind, placebo-controlled study was undertaken between September, 2005, and October, 2008. Patients diagnosed with CMT1A according to clinical examination and confirmation by genotyping were randomly assigned in a 1:1:1 ratio to receive 1 g ascorbic acid per day, 3 g ascorbic acid per day, or placebo. Treatment allocation was based on a computer-generated list of random numbers in blocks of 12, with stratification according to study site and sex; all investigators and participants were unaware of treatment allocation. The primary outcome was the Charcot–Marie–Tooth disease neuropathy score (CMTNS) at 12 months. Analysis was by intention to treat. This study is registered with the Orphanet Database , number ORPHA60779. Findings The median change in CMTNS from baseline to 12 months was 0·5 points (95% CI −0·3 to 1·4) for the placebo group (n=62), 0·7 points (0·0 to 1·4) for the 1 g ascorbic acid group (n=56), and −0·4 points (−1·2 to 0·4) for the 3 g ascorbic acid group (n=61). We did not find any significant difference in these changes between the groups (p=0·14). The occurrence of adverse events did not differ between the groups (p=0·74). Interpretation Ascorbic acid at both doses was safe and well tolerated in adults with CMT1A over 12 months. However, there were no significant differences between the groups and the efficacy of ascorbic acid was not shown. Funding French Ministry of Health (National PHRC 2004) and Association Française Contre les Myopathies.
Genomic rearrangements that give rise to oncogenic gene fusions can offer actionable targets for cancer therapy. Here we present a systematic analysis of oncogenic gene fusions among a clinically ...well-characterized, prospectively collected set of 278 primary colon cancers spanning diverse tumor stages and clinical outcomes. Gene fusions and somatic genetic variations were identified in fresh frozen clinical specimens by Illumina RNA-sequencing, the STAR fusion gene detection pipeline, and GATK RNA-seq variant calling. We considered gene fusions to be pathogenically relevant when recurrent, producing divergent gene expression (outlier analysis), or as functionally important (e.g., kinase fusions). Overall, 2.5% of all specimens were defined as harboring a relevant gene fusion (kinase fusions 1.8%). Novel configurations of
, and
gene fusions resulting from chromosomal translocations were identified. An R-spondin fusion was found in only one tumor (0.35%), much less than an earlier reported frequency of 10% in colorectal cancers. We also found a novel fusion involving USP9X-ERAS formed by chromothripsis and leading to high expression of ERAS, a constitutively active RAS protein normally expressed only in embryonic stem cells. This USP9X-ERAS fusion appeared highly oncogenic on the basis of its ability to activate AKT signaling. Oncogenic fusions were identified only in lymph node-negative tumors that lacked BRAF or KRAS mutations. In summary, we identified several novel oncogenic gene fusions in colorectal cancer that may drive malignant development and offer new targets for personalized therapy.
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It is shown that the onset temperature and the magnitude of thermal events observed during DSC analyses of α-lactose monohydrate can be strongly affected by various treatments such as ageing, manual ...grinding and preheating (cycle of preliminary dehydration and rehydration). In the case of grinding and preheating, the change of dehydration pathways was further investigated by using a suitable combination of characterization techniques, including X-ray powder diffraction (XRPD) performed with a synchrotron source (allowing an accurate Rietveld analysis), scanning electron microscopy (SEM), laser particle size measurements, FTIR spectroscopy and
1H NMR for the determination of β-lactose contents in samples. It appeared that the dehydration mechanism is affected not only by a smaller particle size distribution, but also by residual anisotropic lattice distortions and by the formation of surface defects or high energy surfaces. The fusion–recrystallization process occurring between anhydrous forms of α-lactose at
ca. 170
°C is not significantly affected by grinding, whereas a preheating treatment induces an unexpected large increase of the enthalpy associated with this transition. Our observations and interpretations confirm the important role of water molecules in the crystal cohesion of the title compound and illustrate the necessity to consider the history of each sample for a satisfactory understanding of the physical properties and the behaviour of this important pharmaceutical excipient.
An ultradense genetic linkage map with >10,000 AFLP loci was constructed from a heterozygous diploid potato population. To our knowledge, this is the densest meiotic recombination map ever ...constructed. A fast marker-ordering algorithm was used, based on the minimization of the total number of recombination events within a given marker order in combination with genotyping error-detection software. This resulted in "skeleton bin maps," which can be viewed as the most parsimonious marker order. The unit of distance is not expressed in centimorgans but in "bins." A bin is a position on the genetic map with a unique segregation pattern that is separated from adjacent bins by a single recombination event. Putative centromeres were identified by a strong clustering of markers, probably due to cold spots for recombination. Conversely, recombination hot spots resulted in large intervals of up to 15 cM without markers. The current level of marker saturation suggests that marker density is proportional to physical distance and independent of recombination frequency. Most chromatids (92%) recombined once or never, suggesting strong chiasma interference. Absolute chiasma interference within a chromosome arm could not be demonstrated. Two examples of contig construction and map-based cloning have demonstrated that the marker spacing was in accordance with the expected physical distance: approximately one marker per BAC length. Currently, the markers are used for genetic anchoring of a physical map of potato to deliver a sequence-ready minimal tiling path of BAC contigs of specific chromosomal regions for the potato genome sequencing consortium (http://www.potatogenome.net).
The mid-Ordovician mitrocystitid mitrate Mitrocystella incipiens was one of the most widespread stylophorans in the high latitude Mediterranean Province, with occurrences in the Armorican Massif ...(France), the Iberian Peninsula (Portugal and Spain) and the Prague Basin (Czech Republic), all restricted so far to the late Darriwilian (Hustedograptus teretiusculus Zone). The description of this taxon in the Corréjou Member (Postolonnec Formation) of the Crozon Peninsula (western Brittany, France) not only extends its spatial distribution within the Armorican Massif, but also its stratigraphic range into the mid-Darriwilian (Didymograptus artus Zone). The remarkable preservation of the new material and associated sedimentological evidence both suggest rapid burial by storm deposits.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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