A mass spectrometry workflow for measuring protein turnover rates in vivo

Proteins are continually produced and degraded, to avoid the accumulation of old or damaged molecules and to maintain the efficiency of physiological processes. Despite its importance, protein turnover has been difficult to measure in vivo. Previous approaches to evaluating turnover in vivo have required custom labeling approaches, involved complex mass spectrometry (MS) analyses, or used comparative strategies that do not allow direct quantitative measurements. Here, we describe a robust protocol for quantitative proteome turnover analysis in mice that is based on a commercially available diet for stable isotope labeling of amino acids in mammals (SILAM). We start by discussing fundamental concepts of protein turnover, including different methodological approaches. We then cover in detail the practical aspects of metabolic labeling and explain both the experimental and computational steps that must be taken to obtain accurate in vivo results. Finally, we present a simple experimental workflow that enables measurement of precise turnover rates in a time frame of similar to 4-5 weeks, including the labeling time. We also provide all the scripts needed for the interpretation of the MS results and for comparing turnover across different conditions. Overall, the workflow presented here comprises several improvements in the determination of protein lifetimes with respect to other available methods, including a minimally invasive labeling strategy and a robust interpretation of MS results, thus enhancing reproducibility across laboratories

CMS Forward-Backward MSGC milestone

The CMS MF1 milestone was set in order to evaluate system aspects of the CMS forward-backward MSGC tracker, to check the design and feasibility of mass production and to set up assembly and test procedures. We describe the construction and the experience gained with the operation of a system of 38 MSGC detectors assembled in six multi-substrate detector modules corresponding to the geometry of the forward-backward MSGC tracker in CMS. These modules were equipped with MSGCs mounted side by side, forming a continuous detector surface of about 0.2 m2. Different designs were tried for these modules. The problems encountered are presented with the proposed solutions. Operation conditions for the 38 MSGCs are reported from an exposure to a muon beam at the CERN SPS. Gain uniformity along the wedge-shaped strip pattern and across the detector modules are shown together with the detection efficiency, the spatial resolution, alignment and edge studies

Finding new friends and revisiting old ones – how plant lipid droplets connect with other subcellular structures

Article talks about how the number of described contact sites between different subcellular compartments and structures in eukaryotic cells has increased dramatically in recent years, which has substantially reinforced the well-known premise that these kinds of connections are essential for overall cellular organization. The authors discuss contact sites involving plant lipid droplets (LDs), including LD-endoplasmic reticulum (ER) connections that mediate the biogenesis of new LDs at the ER, LD-peroxisome connections

On the Possibility of Accelerating Positron on an Electron Wake at SABER

A new approach for positron acceleration in non-linear plasma wakefields driven by electron beams is presented. Positrons can be produced by colliding an electron beam with a thin foil target embedded in the plasma. Integration of positron production and acceleration in one stage is realized by a single relativistic, intense electron beam. Simulations with the parameters of the proposed SABER facility [1] at SLAC suggest that this concept could be tested there

Ketogenic diet uncovers differential metabolic plasticity of brain cells

To maintain homeostasis, the body, including the brain, reprograms its metabolism in response to altered nutrition or disease. However, the consequences of these challenges for the energy metabolism of the different brain cell types remain unknown. Here, we generated a proteome atlas of the major central nervous system (CNS) cell types from young and adult mice, after feeding the therapeutically relevant low-carbohydrate, high-fat ketogenic diet (KD) and during neuroinflammation. Under steady-state conditions, CNS cell types prefer distinct modes of energy metabolism. Unexpectedly, the comparison with KD revealed distinct cell type–specific strategies to manage the altered availability of energy metabolites. Astrocytes and neurons but not oligodendrocytes demonstrated metabolic plasticity. Moreover, inflammatory demyelinating disease changed the neuronal metabolic signature in a similar direction as KD. Together, these findings highlight the importance of the metabolic cross-talk between CNS cells and between the periphery and the brain to manage altered nutrition and neurological disease

High-gradient plasma and laser accelerators

Novel high-gradient accelerators have demonstrated acceleration of electrons and positrons with electric field strengths of 1 to > 100 GeV/m. This is about 10 to 1000 times higher than achieved in RF-based accelerators, and as such they have the potential to overcome the limitations associated with RF cavities. Plasma-based accelerators have produced multi-GeV bunches with parameters approaching those suitable for a linear collider. These accelerators offer the prospect of near term, compact and cost-effective particle physics experiments that provide new physics possibilities supporting precision studies and the search for new particles. The expert panel has defined a long term R&D roadmap towards a compact collider with attractive intermediate experiments and studies. A delivery plan for the required R&D has been developed and includes work packages, deliverables, a minimal plan, connections to ongoing projects and an aspirational plan

Commissioning and experiments with a compact transverse deflecting system at FLUTE

A Compact Transverse Deflecting System (Compact-TDS) designed for longitudinal electron bunch diagnostics in the femtosecond regime is presently undergoing commissioning at the Karlsruhe Institute of Technology (KIT). This technique, based on THz streaking using a resonator structure, demands a high level of electron beam controllability and stability at the micrometer scale. To meet these requirements, the linear accelerator FLUTE (Ferninfrarot Linac- Und Test-Experiment) has undergone major upgrades in 2023, incorporating a new RF system equipped with a klystron, RF photoinjector and solenoid magnet. In this contribution, we present first experiments conducted with the Compact-TDS at FLUTE, utilizing the upgraded RF setup

Inverse-Transition Radiation Laser Acceleration Experiments at SLAC

We present a series of laser-driven particle acceleration experiments that are aimed at studying laser-particle acceleration as an inverse-radiation process. To this end we employ a semi-open vacuum setup with a thin planar boundary that interacts with the laser and the electromagnetic field of the electron beam. Particle acceleration from different types of boundaries will be studied and compared to the theoretical expectations from the Inverse-radiation picture and the field path integral method. We plan to measure the particle acceleration effect from transparent, reflective, black, and rough surface boundaries. While the agreement between the two acceleration pictures is straightforward to prove analytically for the transparent and reflective boundaries the equivalence is not clear-cut for the absorbing and rough-surface boundaries. Experimental observation may provide the evidence to distinguish between the models