Molecular profile of ultrastructure changes of the ligamentum flavum related to lumbar spinal canal stenosis

Lumbar spinal canal stenosis (LSCS) is a degenerative disease observed by hypertrophy of the ligamentum flavum (LF) that cause compression of the lumbar neural content. Diabetes mellitus (DM) is a risk factor for the disease and we have shown previously that DM increases the fibrosis and elastic fiber loss in patients with LSCS. The purpose of this study was to find the proteins that play a role in the development of this clinical pathogenesis and the effect of DM on protein expression. LF tissue retrieved from patients diagnosed with LSCS, some were also diagnosed with DM, were compared with LF from patients diagnosed with herniated nucleus pulposus (HNP). The tissues were analyzed by mass spectrometry for proteins profile alteration. We found that LF of LSCS/DM patients exhibited significantly higher levels of proteoglycan proteins and latent transforming growth factor β-binding protein (LTBP2 and LTBP4). Additionally, an increase of HTRA serine protease 1 and insulin-like growth factor binding protein-5 were noted. The higher fibrosis was also associated with proteins related to inflammation and slower tissue repair. Collagen 6 and transforming growth factor inhibitor are related to activation of the anti-inflammatory M2 pathway that is associated with tissue repair. The decrease of these proteins expression in LSCS/DM is associated with increased levels and activation of M1 pro-inflammatory pathways. Interestingly, C3 and C4b members of the complement complex and mannose receptor-like protein (CLEC18) paralogous proteins were detectable solely at the LSCS/DM patients’ samples. Histology analysis shows that inflammatory was induced by the hyperglycemic conditions in diabetic patients involve in altering the matrix compositions. Thus, the protein profiles associated with inflammatory pathways affecting the LF suggested increasing susceptibility of developing the degeneration under hyperglycemic conditions.     

The Molecular and Metabolic Influence of Long Term Agmatine Consumption

Agmatine (AGM), a product of arginine decarboxylation, influences multiple physiologic and metabolic functions. However, the mechanism(s) of action, the impact on whole body gene expression and metabolic pathways, and the potential benefits and risks of long term AGM consumption are still a mystery. Here, we scrutinized the impact of AGM on whole body metabolic profiling and gene expression and assessed a plausible mechanism(s) of AGM action. Studies were performed in rats fed a high fat diet or standard chow. AGM was added to drinking water for 4 or 8 weeks. We used ¹³C or ¹⁵N tracers to assess metabolic reactions and fluxes and real time quantitative PCR to determine gene expression. The results demonstrate that AGM elevated the synthesis and tissue level of cAMP. Subsequently, AGM had a widespread impact on gene expression and metabolic profiling including (a) activation of peroxisomal proliferator-activated receptor-α and its coactivator, PGC1α, and (b) increased expression of peroxisomal proliferator-activated receptor-γ and genes regulating thermogenesis, gluconeogenesis, and carnitine biosynthesis and transport. The changes in gene expression were coupled with improved tissue and systemic levels of carnitine and short chain acylcarnitine, increased β-oxidation but diminished incomplete fatty acid oxidation, decreased fat but increased protein mass, and increased hepatic ureagenesis and gluconeogenesis but decreased glycolysis. These metabolic changes were coupled with reduced weight gain and a curtailment of the hormonal and metabolic derangements associated with high fat diet-induced obesity. The findings suggest that AGM elevated the synthesis and levels of cAMP, thereby mimicking the effects of caloric restriction with respect to metabolic reprogramming.     

Expanding the boundaries of embryonic stem cells

The boundaries of embryonic stem cell (ESC) research have extended considerably in recent years in several?important ways. Alongside a deeper understanding of the pluripotent state, ESCs have been successfully integrated into various fields, such as genomics, epigenetics, and disease modeling. Significant progress in cell fate control has pushed directed differentiation and tissue engineering further than ever before and promoted clinical trials. The geographical distribution of research activity has also expanded, especially for human ESCs. This review outlines these developments and future challenges that remain.     

Multilevel-3D bit patterned magnetic media with 8 signal levels per nanocolumn

This letter presents an experimental study that shows that a 3(rd) physical dimension may be used to further increase information packing density in magnetic storage devices. We demonstrate the feasibility of at least quadrupling the magnetic states of magnetic-based data storage devices by recording and reading information from nanopillars with three magnetically-decoupled layers. Magneto-optical Kerr effect microscopy and magnetic force microscopy analysis show that both continuous (thin film) and patterned triple-stack magnetic media can generate eight magnetically-stable states. This is in comparison to only two states in conventional magnetic recording. Our work further reveals that ferromagnetic interaction between magnetic layers can be reduced by combining Co/Pt and Co/Pd multilayers media. Finally, we are showing for the first time an MFM image of multilevel-3D bit patterned media with 8 discrete signal levels.     

The in vitro survival of human monosomies and trisomies as embryonic stem cells

Chromosomal aneuploidies are responsible for severe human genetic diseases. Aiming at creating models for such disorders, we have generated human embryonic stem cell (hESC) lines from pre-implantation genetic screened (PGS) embryos. The overall analysis of more than 400 aneuploid PGS embryos showed a similar risk of occurrence of monosomy or trisomy for any specific chromosome. However, the generation of hESCs from these embryos revealed a clear bias against monosomies in autosomes. Moreover, only specific trisomies showed a high chance of survival as hESC lines, enabling us to present another categorization of human aneuploidies. Our data suggest that chromosomal haploinsufficiency leads to lethality at very early stages of human development.     

From Causation to Correlation: The Story of Psychosomatic Medicine 1939–1979

This study focuses on the first four decades inthe history of the pioneering journal Psychosomatic Medicine. The goal of thejournal as stated by its founders was to reformmedicine by scientifically reintegrating the``mind' into medicine. However, from itsinception, the editorial members were hauntedby internal ambiguity regarding the nature ofpsychosomatic knowledge. This led to recurrentidentity crises. This study tells the story ofthe complex interplay between internal andexternal forces shaping PsychosomaticMedicine's institutional transitions andepistemological transformations. Itdemonstrates how, despite this continuousinternal confusion, the level of consistencynecessary for gaining legitimacy increasedduring the process of evaluating papers. Theincreased level of standardization coincidedwith a transition in the psychosomaticmovement's epistemological approach: from causation to correlation. The initialattempt to search for causal mechanismslinking the psyche and the soma were replacedby correlational models measuring variousmanifestations of psychological and biologicalphenomena in a way that presupposed andreduplicated the split the founders ironicallysought to supersede.     

Characterization of human embryonic stem cell lines by the International Stem Cell Initiative

The International Stem Cell Initiative characterized 59 human embryonic stem cell lines from 17 laboratories worldwide. Despite diverse genotypes and different techniques used for derivation and maintenance, all lines exhibited similar expression patterns for several markers of human embryonic stem cells. They expressed the glycolipid antigens SSEA3 and SSEA4, the keratan sulfate antigens TRA-1-60, TRA-1-81, GCTM2 and GCT343, and the protein antigens CD9, Thy1 (also known as CD90), tissue-nonspecific alkaline phosphatase and class 1 HLA, as well as the strongly developmentally regulated genes NANOG, POU5F1 (formerly known as OCT4), TDGF1, DNMT3B, GABRB3 and GDF3. Nevertheless, the lines were not identical: differences in expression of several lineage markers were evident, and several imprinted genes showed generally similar allele-specific expression patterns, but some gene-dependent variation was observed. Also, some female lines expressed readily detectable levels of XIST whereas others did not. No significant contamination of the lines with mycoplasma, bacteria or cytopathic viruses was detected.