Unveiling the atomistic and electronic structure of Ni II –NO adduct in a MOF-based catalyst by EPR spectroscopy and quantum chemical modelling †

The nature of the chemical bonding between NO and open-shell NiII ions docked in a metal–organic framework is fully characterized by EPR spectroscopy and computational methods. High-frequency EPR experiments reveal the presence of unsaturated NiII ions displaying five-fold coordination. Upon NO adsorption, in conjunction with advanced EPR methodologies and DFT/CASSCF modelling, the covalency of the metal–NO and metal–framework bonds is directly quantified. This enables unravelling the complex electronic structure of NiII–NO species and retrieving their microscopic structure

Magnetic coupling of divalent metal centers in postsynthetic metal exchanged bimetallic DUT-49 MOFs by EPR spectroscopy

EPR measurements at X- (9.5 GHz), Q- (34 GHz) and W-band (94 GHz) on paddlewheel (PW) type post-synthetic metal exchanged DUT-49(M,M): M- Zn, Mn, Cu MOFs are here reported (DUT–Dresden University of Technology). Temperature-dependent X-band measurements are recorded from T = 7 K to T = 170 K on monometallic DUT-49(Cu), DUT-49(Mn), and bimetallic DUT-49(Cu0.7Zn0.3), DUT-49(Cu0.5Mn0.5) MOFs. In the case of the CuII - CuII dimers in DUT-49(Cu), an isotropic exchange coupling of the metal ions (2J = −240(11) cm−1) determined from the EPR intensity of the S = 1 spin state of the CuII–CuII dimers using the Bleaney Blowers equation. The sign of the found isotropic exchange coupling constant confirms an antiferromagnetic coupling between the cupric ions. Also, the MnII ions in the paddle wheels of DUT-49(Mn) are antiferromagnetically coupled. However, at low temperatures, EPR measurements reveal the presence of CuII and MnII monomers in DUT-49(Cu) and DUT-49(Mn), respectively, either associated with extra framework sites or defective paddle wheels. Otherwise, EPR signals observed for bimetallic DUT-49(Cu0.7Zn0.3) and DUT-49(Cu0.5Mn0.5) MOFs reveal the formation of mixed ion CuII–ZnII and CuII–MnII paddle wheels with SCuZn =1/2 and SCuMn = 2 spin states, respectively

RNA delivery by extracellular vesicles in mammalian cells and its applications.

The term 'extracellular vesicles' refers to a heterogeneous population of vesicular bodies of cellular origin that derive either from the endosomal compartment (exosomes) or as a result of shedding from the plasma membrane (microvesicles, oncosomes and apoptotic bodies). Extracellular vesicles carry a variety of cargo, including RNAs, proteins, lipids and DNA, which can be taken up by other cells, both in the direct vicinity of the source cell and at distant sites in the body via biofluids, and elicit a variety of phenotypic responses. Owing to their unique biology and roles in cell-cell communication, extracellular vesicles have attracted strong interest, which is further enhanced by their potential clinical utility. Because extracellular vesicles derive their cargo from the contents of the cells that produce them, they are attractive sources of biomarkers for a variety of diseases. Furthermore, studies demonstrating phenotypic effects of specific extracellular vesicle-associated cargo on target cells have stoked interest in extracellular vesicles as therapeutic vehicles. There is particularly strong evidence that the RNA cargo of extracellular vesicles can alter recipient cell gene expression and function. During the past decade, extracellular vesicles and their RNA cargo have become better defined, but many aspects of extracellular vesicle biology remain to be elucidated. These include selective cargo loading resulting in substantial differences between the composition of extracellular vesicles and source cells; heterogeneity in extracellular vesicle size and composition; and undefined mechanisms for the uptake of extracellular vesicles into recipient cells and the fates of their cargo. Further progress in unravelling the basic mechanisms of extracellular vesicle biogenesis, transport, and cargo delivery and function is needed for successful clinical implementation. This Review focuses on the current state of knowledge pertaining to packaging, transport and function of RNAs in extracellular vesicles and outlines the progress made thus far towards their clinical applications

Comparison of double sensor, skin, and rectal temperature recordings for determining circadian rhythm

Introduction In chronobiology studies, the circadian rhythm of core body temperature has often been monitored via rectal temperature recordings. Compliance with rectal recordings, however, limits voluntary participation and prevents a broader spectrum of investigations. With the progress of technology, systems have been developed which allow a measurement of the core body temperature from an intact skin surface, such as the Double Sensor [1], a skin surface temperature and heat-flux combining device. Studies regarding how well such systems reflect the circadian rhythm of core body temperature, however, are lacking. Material & Methods As part of the 2nd Berlin BedRest Study (BBR2-2), subjects underwent micro-g simulated conditions, i.e. 6\ub0 headdown tilt bed-rest. On bed-rest day 49, 24 hours temperature profiles were obtained in seven healthy men by a single skin surface temperature sensor and the Double Sensor, each placed at forehead (Tfhd, DSfhd) and sternum (Tste, DSste), and by a rectal probe (Trec). The degree of parallelism between measured temperature variables was assessed by calculating the Pearson correlation coefficient r. Rhythm characteristics determined by fitting a single cosine curve included MESOR, amplitude, and acrophase, and were statistically tested for significance by Student's paired t-test. Results Averaged value (\ub1 SD) of Pearson\u2019s r was .867 (.059), .797 (.097), .519 (.373), -.021 (.549) for correlation between Trec with DSfhd, Tfhd, DSste, and Tste, respectively. The correlation mean demonstrated a good parallelism between Trec and temperatures obtained from the forehead. Regarding the rhythm parameters MESOR, amplitude, and acrophase, no significant difference was found between Trec and DSfhd, but between Tfhd and DSfhd as well as between Tfhd and Trec. Discussion & Conclusions Not the skin surface temperature recordings, but the temperatures of the Double Sensor from the forehead seem promising for determining the circadian rhythm of core body temperature in occupational and environmental medicine on earth and space, where the use of rectal probes is not feasible or desired

Phase shifts of circadian core body temperature profiles during Mars500

A growing body of research indicates that a misalignment of circadian rhythms can be detrimental to mental and physical health. Long-term space missions may also potentially alter circadian rhythms, and pose a critical risk to crew health and safety. The long-term impact of isolation and confinement on circadian rhythms has not been fully characterized. We here assessed the impact of the Mars500 study on the circadian phase of core body temperature (CBT). CBT was recorded continuously for 24 h at the forehead using a recently proposed heat-flux technique (Double Sensor) [1] before (BDC) and during (ISO-20, ISO-60, ISO-140, ISO-200, ISO-260, ISO-320, ISO-400, ISO-460) the mission. Each recording was then subjected to cosinor analysis to determine acrophase for each subject and session. A linear mixed model treating \u201cTime\u201d as fixed e\u21b5ect was fit to phase, including random e\u21b5ects (intercepts and slopes) to account for individual subject variation. To analyze whether the rate of change in CBT was characterized by nonlinear changes over time, quadratic and cubic models were also considered. In spite of substantial inter-individual variation, visual inspection of the data indicated a phase advance during the first half of the mission (+1.4 h), after which phase returned to baseline again (phase delay of about -1.2 h relative to first mission half). At ISO-460 phase sharply advanced again to similar levels observed during the first half of the mission. This pattern was confirmed by significant linear, quadratic and cubic components of the mixed model (P<0.05). This third degree polynomial trend is well in line with recent data, showing substantial di\u21b5erences for sleep-wake cycles between the first and last the part of the 520-d mission [2]. We suggest that this specific pattern is related to a highly controlled diet, which was administered during the first half of the mission. This diet required very strict meal times, which are well known to be strong nonphotic cues for circadian entrainment [3]. In contrast, we speculate that the sudden phase advance after 400 mission days could be related to the exposure of blue light, which was exclusively employed during days 439-499 only. In conclusion, the present results indicate that long-term isolation can induce significant changes in the circadian timing system, which might be attributed to specific nonphotic and photic cues of the Mars500 experiment. [1] Respir Physiol Neurobiol, 169 (2009) S63-S68 [2] PNAS, 110 (2013) 2635-2640 [3] Science, 320 (2008) 1074\u2013107