Downramp-assisted underdense photocathode electron bunch generation in plasma wakefield accelerators

It is shown that the requirements for high quality electron bunch generation and trapping from an underdense photocathode in plasma wakefield accelerators can be substantially relaxed through localizing it on a plasma density downramp. This depresses the phase velocity of the accelerating electric field until the generated electrons are in phase, allowing for trapping in shallow trapping potentials. As a consequence the underdense photocathode technique is applicable by a much larger number of accelerator facilities. Furthermore, dark current generation is effectively suppressed.Comment: 4 pages, 3 figure

Genetic versus Non-Genetic Regulation of miR-103, miR-143 and miR-483-3p Expression in Adipose Tissue and Their Metabolic Implications-A Twin Study.

Murine models suggest that the microRNAs miR-103 and miR-143 may play central roles in the regulation of subcutaneous adipose tissue (SAT) and development of type 2 diabetes (T2D). The microRNA miR-483-3p may reduce adipose tissue expandability and cause ectopic lipid accumulation, insulin resistance and T2D. We aimed to explore the genetic and non-genetic factors that regulate these microRNAs in human SAT, and to investigate their impact on metabolism in humans. Levels of miR-103, miR-143 and miR-483-3p were measured in SAT biopsies from 244 elderly monozygotic and dizygotic twins using real-time PCR. Heritability estimates were calculated and multiple regression analyses were performed to study associations between these microRNAs and measures of metabolism, as well as between these microRNAs and possible regulating factors. We found that increased BMI was associated with increased miR-103 expression levels. In addition, the miR-103 levels were positively associated with 2 h plasma glucose levels and hemoglobin A1c independently of BMI. Heritability estimates for all three microRNAs were low. In conclusion, the expression levels of miR-103, miR-143 and miR-483-3p in adipose tissue are primarily influenced by non-genetic factors, and miR-103 may be involved in the development of adiposity and control of glucose metabolism in humans

Floral volatiles from Clarkia breweri and C. concinna ( Onagraceae ): Recent evolution of floral scent and moth pollination

Clarkia breweri ( Onagraceae ) is the only species known in its genus to produce strong floral fragrance and to be pollinated by moths. We used gas chromatography-mass spectrometry (GC-MS) to identify 12 abundant compounds in the floral headspace from two inbred lines of C. breweri. These volatiles are derived from two biochemical pathways, one producing acyclic monoterpenes and their oxides, the other leading from phenylalanine to benzoate and its derivatives. Linalool and linalool oxide (pyran form) were the most abundant monoterpenoids, while linalool oxide (furan form) was present at lower concentrations. Of the aromatic compounds detected, benzyl acetate was most abundant, whereas benzyl benzoate, eugenol, methyl salicylate, and vanillin were present as minor constituents in all floral samples. The two inbred C. breweri lines differed for the presence of the additional benzenoid compounds isoeugenol, methyleugenol, methylisoeugenol, and veratraldehyde. We also analyzed floral headspace from C. concinna , the likely progenitor of C. breweri , whose flowers are odorless to the human nose. Ten volatiles (mostly terpenoids) were detected at low concentrations, but only when headspace was collected from 20 or more flowers at a time. Trans-β-ocimene was the most abundant floral compound identified from this species. Our data are consistent with the hypothesized recent evolution of floral scent production and moth pollination in C. breweri.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41639/1/606_2004_Article_BF00983216.pd

Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.

Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field

Genetic versus Non-Genetic Regulation of miR-103, miR-143 and miR-483-3p Expression in Adipose Tissue and Their Metabolic Implications-A Twin Study.

Murine models suggest that the microRNAs miR-103 and miR-143 may play central roles in the regulation of subcutaneous adipose tissue (SAT) and development of type 2 diabetes (T2D). The microRNA miR-483-3p may reduce adipose tissue expandability and cause ectopic lipid accumulation, insulin resistance and T2D. We aimed to explore the genetic and non-genetic factors that regulate these microRNAs in human SAT, and to investigate their impact on metabolism in humans. Levels of miR-103, miR-143 and miR-483-3p were measured in SAT biopsies from 244 elderly monozygotic and dizygotic twins using real-time PCR. Heritability estimates were calculated and multiple regression analyses were performed to study associations between these microRNAs and measures of metabolism, as well as between these microRNAs and possible regulating factors. We found that increased BMI was associated with increased miR-103 expression levels. In addition, the miR-103 levels were positively associated with 2 h plasma glucose levels and hemoglobin A1c independently of BMI. Heritability estimates for all three microRNAs were low. In conclusion, the expression levels of miR-103, miR-143 and miR-483-3p in adipose tissue are primarily influenced by non-genetic factors, and miR-103 may be involved in the development of adiposity and control of glucose metabolism in humans

Merging Molecular Electron Microscopy and Mass Spectrometry by Carbon Film-assisted Endoproteinase Digestion*

Many fundamental processes in the cell are performed by complex macromolecular assemblies that comprise a large number of proteins. Numerous macromolecular assemblies are structurally rather fragile and may suffer during purification, resulting in the partial dissociation of the complexes. These limitations can be overcome by chemical fixation of the assemblies, and recently introduced protocols such as gradient fixation during ultracentrifugation (GraFix) offer advantages for the analysis of fragile macromolecular assemblies. The irreversible fixation, however, is thought to render macromolecular samples useless for studying their protein composition. We therefore developed a novel approach that possesses the advantages of fixation for structure determination by single particle electron microscopy while still allowing a correlative compositional analysis by mass spectrometry. In this method, which we call “electron microscopy carbon film-assisted digestion”, macromolecular assemblies are chemically fixed and then adsorbed onto electron microscopical carbon films. Parallel, identically prepared specimens are then subjected to structural investigation by electron microscopy and proteomics analysis by mass spectrometry of the digested sample. As identical sample preparation protocols are used for electron microscopy and mass spectrometry, the results of both methods can directly be correlated. In addition, we demonstrate improved sensitivity and reproducibility of electron microscopy carbon film-assisted digestion as compared with standard protocols. We show that sample amounts of as low as 50 fmol are sufficient to obtain a comprehensive protein composition of two model complexes. We suggest our approach to be an optimization technique for the compositional analysis of macromolecules by mass spectrometry in general

Higher gene expression stability during aging in long-lived giant mole-rats than in short-lived rats

Many aging-associated physiological changes are known to occur in short- and long-lived species with different trajectories. Emerging evidence suggests that numerous life history trait differences between species are based on interspecies variations in gene expression. Little information is available, however, about differences in transcriptome changes during aging between mammals with diverging lifespans. For this reason, we studied the transcriptomes of five tissue types and two age cohorts of two similarly sized rodent species with very different lifespans: laboratory rats (Rattus norvegicus) and giant mole-rats (Fukomys mechowii), with maximum lifespans of 3.8 and more than 20 years, respectively. Our findings show that giant mole-rats exhibit higher gene expression stability during aging than rats. Although well-known aging signatures were detected in all tissue types of rats, they were found in only one tissue type of giant mole-rats. Furthermore, many differentially expressed genes that were found in both species were regulated in opposite directions during aging. This suggests that expression changes which cause aging in short-lived species are counteracted in long-lived species. Taken together, we conclude that expression stability in giant mole rats (and potentially in African mole-rats in general) may be one key factor for their long and healthy life