Cotranslational biogenesis of membrane proteins in bacteria

Nascent polypeptides emerging from the ribosome during translation are rapidly scanned and processed by ribosome-associated protein biogenesis factors (RPBs). RPBs cleave the N-terminal formyl and methionine groups, assist cotranslational protein folding, and sort the proteins according to their cellular destination. Ribosomes translating inner- membrane proteins are recognized and targeted to the translocon with the help of the signal recognition particle, SRP, and SRP receptor, FtsY. The growing nascent peptide is then inserted into the phospholipid bilayer at the translocon, an inner-membrane protein complex consisting of SecY, SecE, and SecG. Folding of membrane proteins requires that transmembrane helices (TMs) attain their correct topology, the soluble domains are inserted at the correct (cytoplasmic or periplasmic) side of the membrane, and – for polytopic membrane proteins – the TMs find their interaction partner TMs in the phospholipid bilayer. This review describes the recent progress in understanding how growing nascent peptides are processed and how inner-membrane proteins are targeted to the translocon and find their correct orientation at the membrane, with the focus on biophysical approaches revealing the dynamics of the process. We describe how spontaneous fluctuations of the translocon allow diffusion of TMs into the phospholipid bilayer and argue that the ribosome orchestrates cotranslational targeting not only by providing the binding platform for the RPBs or the translocon, but also by helping the nascent chains to find their correct orientation in the membrane. Finally, we present the auxiliary role of YidC as a chaperone for inner-membrane proteins. We show how biophysical approaches provide new insights into the dynamics of membrane protein biogenesis and raise new questions as to how translation modulates protein folding

Lateral gate dynamics of the bacterial translocon during cotranslational membrane protein insertion

During synthesis of membrane proteins, transmembrane segments (TMs) of nascent proteins emerging from the ribosome are inserted into the central pore of the translocon (SecYEG in bacteria) and access the phospholipid bilayer through the open lateral gate formed of two helices of SecY. Here we use single-molecule fluorescence resonance energy transfer to monitor lateral-gate fluctuations in SecYEG embedded in nanodiscs containing native membrane phospholipids. We find the lateral gate to be highly dynamic, sampling the whole range of conformations between open and closed even in the absence of ligands, and we suggest a statistical model-free approach to evaluate the ensemble dynamics. Lateral gate fluctuations take place on both short (submillisecond) and long (subsecond) timescales. Ribosome binding and TM insertion do not halt fluctuations but tend to increase sampling of the open state. When YidC, a constituent of the holotranslocon, is bound to SecYEG, TM insertion facilitates substantial opening of the gate, which may aid in the folding of YidC-dependent polytopic membrane proteins. Mutations in lateral gate residues showing in vivo phenotypes change the range of favored states, underscoring the biological significance of lateral gate fluctuations. The results suggest how rapid fluctuations of the lateral gate contribute to the biogenesis of inner-membrane proteins

Dynamic Behavior of a Sensible-heat based Thermal Energy Storage

AbstractIn this paper, a mathematical model is developed to study the behavior of thermal energy storage (TES) under operation in the particular case of Adiabatic Compressed Air Energy Storage (A CAES). The A CAES consists of storing the available extra electrical energy of the electricity network in a form of compressed air (in a cavern) to discharge it during peak periods. The TES sub-system is used to charge and discharge the corresponding heat of compression, leading to a quasi adiabatic mode and an increase in the overall electricity storage efficiency (roughly from 50 to 70%) compared to diabatic CAES. The mathematical model has been converted into a computer simulation program with all the effective parameters of heat transfer in the storage reservoir. This model used to define a geometry reservoir able of storing a given power and restore it while maintaining a required temperature level at the output of unit. The influence of the input and output parameters on the storage efficiency is studied. The results illustrate the behavior of the storage reservoir under dynamic mode

High Frequency top-down Junction-less Silicon Nanowire Resonators

We report here the first realization of top-down silicon nanowires (SiNW) transduced by both junction-less field effect transistor (FET) and the piezoresistive (PZR) effect. The suspended SiNWs are among the smallest top-down SiNWs reported to date, featuring widths down to ~20nm. This has been achieved thanks to a 200mm-wafer-scale, VLSI process fully amenable to monolithic CMOS co-integration. Thanks to the very small dimensions, the conductance of the silicon nanowire can be controlled by a nearby electrostatic gate. Both the junction-less FET and the previously demonstrated PZR transduction have been performed with the same SiNW. These self-transducing schemes have shown similar signal-to-background ratios, and the PZR transduction has exhibited a relatively higher output signal. Allan deviation AD of the same SiNW has been measured with both schemes, and we obtain AD~20ppm for the FET detection and AD~3ppm for the PZR detection at room temperature and low pressure. Orders of magnitude improvements are expected from tighter electrostatic control via changes in geometry and doping level, as well as from CMOS integration. The compact, simple topology of these elementary SiNW resonators opens up new paths towards ultra-dense arrays for gas and mass sensing, time keeping or logic switching systems in SiNW-CMOS platform

Proenkephalin A 119-159 (Penkid) Is an Early Biomarker of Septic Acute Kidney Injury: The Kidney in Sepsis and Septic Shock (Kid-SSS) Study

Introduction: Sepsis is the leading cause of acute kidney injury (AKI) in critically ill patients. The Kidney in Sepsis and Septic Shock (Kid-SSS) study evaluated the value of proenkephalin A 119-159 (penkid)—a sensitive biomarker of glomerular function, drawn within 24 hours upon intensive care unit (ICU) admission and analyzed using a chemiluminescence immunoassay—for kidney events in sepsis and septic shock. Methods: The Kid-SSS study was a substudy of Adrenomedullin and Outcome in Severe Sepsis and Septic Shock (AdrenOSS) (NCT02393781), a prospective, observational, multinational study including 583 patients admitted to the intensive care unit with sepsis or septic shock and a validation cohort of 525 patients from the French and euRopean Outcome reGistry in Intensive Care Units (FROG-ICU) study. The primary endpoint was major adverse kidney events (MAKEs) at day 7, composite of death, renal replacement therapy, and persistent renal dysfunction. The secondary endpoints included AKI, transient AKI, worsening renal function (WRF), and 28-day mortality. Results: Median age was 66 years (interquartile range 55–75), and 28-day mortality was 22% (95% confidence interval [CI] 19%−25%). Of the patients, 293 (50.3%) were in shock upon ICU admission. Penkid was significantly elevated in patients with MAKEs, persistent AKI, and WRF (median = 65 [IQR = 45–106] vs. 179 [114–242]; 53 [39–70] vs. 133 [79–196] pmol/l; and 70 [47–121] vs. 174 [93–242] pmol/l, all P < 0.0001), also after adjustment for confounding factors (adjusted odds ratio = 3.3 [95% CI = 1.8–6.0], 3.9 [95% CI = 2.1–7.2], and 3.4 [95% CI = 1.9–6.2], all P < 0.0001). Penkid increase preceded elevation of serum creatinine with WRF and was low in renal recovery. Conclusion: Admission penkid concentration was associated with MAKEs, AKI, and WRF in a timely manner in septic patients

Beyond linear coupling in microwave optomechanics

We explore the nonlinear dynamics of a cavity optomechanical system. Our realization consisting of a drumhead nano-electro-mechanical resonator (NEMS) coupled to a microwave cavity, allows for a nearly ideal platform to study the nonlinearities arising purely due to radiation-pressure physics. Experiments are performed under a strong microwave Stokes pumping which triggers mechanical self-sustained oscillations. We analyze the results in the framework of an extended nonlinear optome-chanical theory, and demonstrate that quadratic and cubic coupling terms in the opto-mechanical Hamiltonian have to be considered. Quantitative agreement with the measurements is obtained considering only genuine geometrical nonlinearities: no thermo-optical instabilities are observed, in contrast with laser-driven systems. Based on these results, we describe a method to quantify nonlin-ear properties of microwave optomechanical devices. Such a technique, available now in the quantum electro-mechanics toolbox, but completely generic, is mandatory for the development of new schemes where higher-order coupling terms are proposed as a new resource, like Quantum Non-Demolition measurements, or in the search for new fundamental quantum signatures, like Quantum Gravity. We also find that the motion imprints a wide comb of extremely narrow peaks in the microwave output field, which could also be exploited in specific microwave-based measurements, potentially limited only by the quantum noise of the optical and the mechanical fields for a ground-state cooled NEMS device

A calibration method for broad-bandwidth cavity enhanced absorption spectroscopy performed with supercontinuum radiation

An efficient calibration method has been developed for broad-bandwidth cavity enhanced absorption spectroscopy. The calibration is performed using phase shift cavity ring-down spectroscopy, which is conveniently implemented through use of an acousto-optic tunable filter (AOTF). The AOTF permits a narrowband portion of the SC spectrum to be scanned over the full high-reflectivity bandwidth of the cavity mirrors. After calibration the AOTF is switched off and broad-bandwidth CEAS can be performed with the same light source without any loss of alignment to the set-up. We demonstrate the merits of the method by probing transitions of oxygen molecules O-2 and collisional pairs of oxygen molecules (O-2)(2) in the visible spectral range

On Polynomial Stability of Coupled Partial Differential Equations in 1D

We study the well-posedness and asymptotic behaviour of selected PDE-PDE and PDE-ODE systems on one-dimensional spatial domains, namely a boundary coupled wave-heat system and a wave equation with a dynamic boundary condition. We prove well-posedness of the models and derive rational decay rates for the energy using an approach where the coupled systems are formulated as feedback interconnections of impedance passive regular linear systems.Comment: 12 pages, 1 figure, accepted for publication in the Proceedings of "Semigroups of Operators: Theory and Applications", Kazimierz Dolny, Poland, October 201

Gas emissions and active tectonics within the submerged section of the North Anatolian Fault zone in the Sea of Marmara

The submerged section of the North Anatolian fault within the Marmara Sea was investigated using acoustic techniques and submersible dives. Most gas emissions in the water column were found near the surface expression of known active faults. Gas emissions are unevenly distributed. The linear fault segment crossing the Central High and forming a seismic gap – as it has not ruptured since 1766, based on historical seismicity, exhibits relatively less gas emissions than the adjacent segments. In the eastern Sea of Marmara, active gas emissions are also found above a buried transtensional fault zone, which displayed micro-seismic activity after the 1999 events. Remarkably, this zone of gas emission extends westward all along the southern edge of Cinarcik basin, well beyond the zone where 1999 aftershocks were observed. The long term monitoring of gas seeps could hence be highly valuable for the understanding of the evolution of the fluid-fault coupling processes during the earthquake cycle within the Marmara Sea

Biomarker discovery and redundancy reduction towards classification using a multi-factorial MALDI-TOF MS T2DM mouse model dataset

Diabetes like many diseases and biological processes is not mono-causal. On the one hand multifactorial studies with complex experimental design are required for its comprehensive analysis. On the other hand, the data from these studies often include a substantial amount of redundancy such as proteins that are typically represented by a multitude of peptides. Coping simultaneously with both complexities (experimental and technological) makes data analysis a challenge for Bioinformatics