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- Stefanucci, Luca, et al.
(author)
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SMIM1 absence is associated with reduced energy expenditure and excess weight
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In: Med (New York, N.Y.). - 2666-6340.
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Journal article (peer-reviewed)abstract
- BACKGROUND: Obesity rates have nearly tripled in the past 50 years, and by 2030 more than 1 billion individuals worldwide are projected to be obese. This creates a significant economic strain due to the associated non-communicable diseases. The root cause is an energy expenditure imbalance, owing to an interplay of lifestyle, environmental, and genetic factors. Obesity has a polygenic genetic architecture; however, single genetic variants with large effect size are etiological in a minority of cases. These variants allowed the discovery of novel genes and biology relevant to weight regulation and ultimately led to the development of novel specific treatments.METHODS: We used a case-control approach to determine metabolic differences between individuals homozygous for a loss-of-function genetic variant in the small integral membrane protein 1 (SMIM1) and the general population, leveraging data from five cohorts. Metabolic characterization of SMIM1 -/- individuals was performed using plasma biochemistry, calorimetric chamber, and DXA scan. FINDINGS: We found that individuals homozygous for a loss-of-function genetic variant in SMIM1 gene, underlying the blood group Vel, display excess body weight, dyslipidemia, altered leptin to adiponectin ratio, increased liver enzymes, and lower thyroid hormone levels. This was accompanied by a reduction in resting energy expenditure.CONCLUSION: This research identified a novel genetic predisposition to being overweight or obese. It highlights the need to investigate the genetic causes of obesity to select the most appropriate treatment given the large cost disparity between them.FUNDING: This work was funded by the National Institute of Health Research, British Heart Foundation, and NHS Blood and Transplant.
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| 3. |
- Pruim, Peter, et al.
(author)
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Methacrylate monolithic stationary phases for gradient elution separations in microfluidic devices
- 2011
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In: Journal of Chromatography A. - : Elsevier BV. - 0021-9673 .- 1873-3778. ; 1218:31, s. 5292-5297
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Journal article (peer-reviewed)abstract
- Methacrylate monolithic stationary phases were produced in fused-silica chips by UV initiation. Poly(butyl methacrylate-co-ethylene dimethacrylate) (BMA) and poly(lauryl methacrylate-co-ethylene dimethacrylate) (LMA) monoliths containing 30, 35 and 40% monomers were evaluated for the separation of peptides under gradient conditions. The peak capacity was used as an objective tool for the evaluation of the separation performance. LMA monoliths of the highest density gave the highest peak capacities (approximate to 40) in gradients of 15 min and all LMA monoliths gave higher peak capacities than the BMA monoliths with the same percentage of monomers. Increasing the gradient duration to 30 min did not increase the peak capacity significantly. However, running fast (5 min) gradients provides moderate peak capacities (approximate to 20) in a short time. Due to the system dead volume of 1 mu L and the low bed volume of the chip, early eluting peptides migrated over a significant part of the column during the dwell time under isocratic conditions. It was shown that this could explain an increased band broadening on the monolithic stationary phase materials used. The effect is stronger with BMA monoliths, which partly explains the inferior performance of this material with respect to peak capacity. The configuration of the connections on the chip appeared to be critical when fast analyses were performed at pressures above 20 bar. (C) 2011 Elsevier B.V. All rights reserved.
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| 4. |
- Aminlashgari, Nina, 1984-
(author)
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LDI-MS strategies for analysis of polymer degradation products, additives and drugs
- 2014
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Doctoral thesis (other academic/artistic)abstract
- The advancement of mass spectrometry (MS) has been and continues to be a prominent analytical technique for highly accurate determination of analytes. The goal of this thesis was to develop new laser desorption ionization-mass spectrometric (LDI-MS) methods for analysis of polymer degradation products, additives and drugs. Modifications in the sample preparation were evaluated in the presence and absence of surface assisting materials. Various nanoparticles were evaluated as effective absorbents for energy transfer in the LDI procedure of the small molecules.In paper I and II, LDI-MS methods were developed for following the progression of chemical reactions. First, the procedure to optimize microwave assisted hydrothermal degradation products of cellulose were analyzed; second, the synthesis of glucose hexanoate ester plasticizers was monitored as a function of reaction time. The LDI-MS method provided rapid detection for the elucidation of the chemical products and their relative ratios. In contrast, the electrospray ionization-mass spectrometry (ESI-MS) analysis produced a noisy spectrum primarily containing peaks from salt clusters. A surface assisted laser desorption ionization-mass spectrometry (SALDI-MS) method was developed in paper III enabling the identification of poly(e-caprolactone) and its degradation products by using nanoparticles as the substrate. Similar analysis by matrix assisted laser desorption ionization-mass spectrometry (MALDI-MS) was not as successful due to convolution of the analyte peaks with clusters released from the matrix. ESI-MS analysis verified the SALDI-MS method as comparable degradation product patterns were observed. Furthermore, the possibility of using polylactide based nanocomposites as surfaces in the analysis of drugs was evaluated in paper IV. An advantage was the ease of handling compared to the use of free nanoparticles. Paper V introduces the potential of direct examination of oxygen plasma modified parylene C surfaces by a LDI-MS methodology.
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| 5. |
- Woldegiorgis, Andreas, 1968-
(author)
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Fabrication of new silica nano structures and development of new concepts for MALDI-TOF mass spectrometry
- 2004
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Doctoral thesis (other academic/artistic)abstract
- A technique to alter the morphology of the inner surface of fused silica capillaries has been developed. The internal surface area is enlarged by means of nano-wires of silica, which are grown from the capillary walls. The growth is initiated by the decomposition of the etchant precursor 2-chloro-1,1,2–trifluoroethylmethyl ether at elevated temperature and pressure. It is suggested that the formation of the nano-wires is a process where hydrogen fluoride is continuously consumed and re-liberated. The amorphous bulk silica wall is dissolved, vaporized and finally condensed, yielding a directional re-formation of silica into nano-wire structures. The unidirectional growth of the nano-wires seems to follow the well-known vapor-liquid-solid (VLS) mechanism since characteristic attributes of the VLS mechanism can be observed in the modified capillaries, such as spherical particles terminating each nano-wire. An alternative procedure was developed based on non-isothermal etching which enabled nano-wire outgrowth in fused silica capillaries with internal diameters exceeding 5 µm. The etched and modified capillaries are expected to be suitable for fluidic applications where a higher surface-to-volume ratio is beneficial, such as open tubular liquid chromatography as well as solid-phase micro-reactors and catalysis including enzymatic reactions. The last part of the thesis describes new techniques developed for matrix-assisted laser desorption/ionization (MALDI) mass spectrometry. A set of novel matrices based on polymers/oligomers of benzodioxins and thiophenes has been introduced. Using this approach, which has been given the name Polymer-Assisted Laser Desorption/Ionization (PALDI), the low m/z-range of the mass spectrum, from 180 to 1.000 Da, could be used without the abundant chemical noise which normally disturbs such MALDI-MS spectra. Some of the PALDI matrices also showed excellent behavior in the analysis of low molecular weight polymers. A methodology based on non-linear regression of cumulative frequency distributions in polymers has been developed to compare and evaluate different matrix/polymer/cation agent sample combinations for MALDI and PALDl-MS analyses of low molecular weight polymers.
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