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2022 ◽  
Vol 206 ◽  
pp. 112624
Author(s):  
Kai Cheng ◽  
Yunhua Chang ◽  
Yaqiong Kuang ◽  
Rehana Khan ◽  
Zhong Zou

2022 ◽  
Vol 284 ◽  
pp. 116993
Author(s):  
Riccardo Salvio ◽  
Saverio Santi ◽  
Antonio Toffoletti ◽  
Mauro Bassetti
Keyword(s):  

2022 ◽  
Vol 55 (1) ◽  
Author(s):  
Diandra Doppler ◽  
Mohammad T. Rabbani ◽  
Romain Letrun ◽  
Jorvani Cruz Villarreal ◽  
Dai Hyun Kim ◽  
...  

Serial femtosecond crystallography (SFX) is a powerful technique that exploits X-ray free-electron lasers to determine the structure of macromolecules at room temperature. Despite the impressive exposition of structural details with this novel crystallographic approach, the methods currently available to introduce crystals into the path of the X-ray beam sometimes exhibit serious drawbacks. Samples requiring liquid injection of crystal slurries consume large quantities of crystals (at times up to a gram of protein per data set), may not be compatible with vacuum configurations on beamlines or provide a high background due to additional sheathing liquids present during the injection. Proposed and characterized here is the use of an immiscible inert oil phase to supplement the flow of sample in a hybrid microfluidic 3D-printed co-flow device. Co-flow generation is reported with sample and oil phases flowing in parallel, resulting in stable injection conditions for two different resin materials experimentally. A numerical model is presented that adequately predicts these flow-rate conditions. The co-flow generating devices reduce crystal clogging effects, have the potential to conserve protein crystal samples up to 95% and will allow degradation-free light-induced time-resolved SFX.


Author(s):  
Shawutijiang Sidikejiang ◽  
Philipp Henning ◽  
Philipp Horenburg ◽  
Heiko Bremers ◽  
Uwe Rossow ◽  
...  

Abstract We compare the low-temperature photoluminescence (PL) intensities of a range of GaInN/GaN quantum well (QW) structures under identical excitation conditions, mounting the samples side by side. Normalizing the measured intensity to the absorbed power density in the QWs, we find that low-temperature PL efficiencies of several samples, which show close to 100% IQE in time-resolved PL, saturate at nearly an identical value. Of course, this is strong indicative of being 100% IQE at low temperature for those efficient samples. Using the low-temperature PL efficiency as a ``Reference'', on the other hand, we observe not only the effects of temperature-independent non-radiative losses on the low-temperature IQE, but also are able to determine the IQE of arbitrary samples on an absolute scale. Furthermore, we prove the experimental results by comparing the low-temperature efficiencies of a sample with an initial 100% IQE after intentionally introducing structural defects with argon-implantation.


2022 ◽  
Vol 23 (2) ◽  
pp. 911
Author(s):  
Andrea Hanel ◽  
Carsten Carlberg

Peripheral blood mononuclear cells (PBMCs) belong to the innate and adaptive immune system and are highly sensitive and responsive to changes in their systemic environment. In this study, we focused on the time course of transcriptional changes in freshly isolated human PBMCs 4, 8, 24 and 48 h after onset of stimulation with the active vitamin D metabolite 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3). Taking all four time points together, 662 target genes were identified and segregated either by time of differential gene expression into 179 primary and 483 secondary targets or by driver of expression change into 293 direct and 369 indirect targets. The latter classification revealed that more than 50% of target genes were primarily driven by the cells' response to ex vivo exposure than by the nuclear hormone and largely explained its down-regulatory effect. Functional analysis indicated vitamin D’s role in the suppression of the inflammatory and adaptive immune response by down-regulating ten major histocompatibility complex class II genes, five alarmins of the S100 calcium binding protein A family and by affecting six chemokines of the C-X-C motif ligand family. Taken together, studying time-resolved responses allows to better contextualize the effects of vitamin D on the immune system.


2022 ◽  
Author(s):  
Jia-Wei Wang ◽  
Xian Zhang ◽  
Michael Karnahl ◽  
Zhi-Mei Luo ◽  
Zizi Li ◽  
...  

Abstract The utilization of a fully noble-metal-free system for photocatalytic CO2 reduction remains a fundamental challenge, demanding the precise design of photosensitizers and catalysts, as well as the exploitation of their intermolecular interactions to facilitate electron delivery. Herein, we have implemented triple modulations on catalyst, photosensitizer and coordinative interaction between them for high-performance light-driven CO2 reduction. In this study, heteroleptic copper and cobalt phthalocyanine complexes were selected as photosensitizers and catalysts, respectively. An over ten-fold improvement in light-driven reduction of CO2 to CO is achieved for the catalysts with appending electron-withdrawing substituents for optimal CO-desorption ability. In addition, pyridine substituents were implanted at the backbone of the phenanthroline moiety of the Cu(I) photosensitizers and the effect of their axial coordinative interaction with the catalyst was tested. The combined results of 1H NMR titration experiment, steady-state/transient photoluminescence, and transient absorption spectroscopy confirm the coordinative interaction and reductive quenching pathway in photocatalysis corroboratively. It has been found that the catalytic performances of the coordinatively interacted systems are unexpectedly reverse to those with the pyridine-free Cu(I) photosensitizers. Moreover, the latter system enables a very high quantum efficiency up to 63.5% at 425 nm with a high selectivity exceeding 99% for CO2-to-CO conversion. As determined by time-resolved X-ray absorption spectroscopy and DFT calculation, the replacement of phenyl by pyridyl groups in the Cu(I) photosensitizer favors a stronger flattening and larger torsional angle change of the overall excited state geometry upon photoexcitation, which explains the decreased lifetime of the triplet excited state. Our work promotes the systematic multi-pathway optimizations on the catalyst, photosensitizer and their interactions for advanced CO2 photoreduction.


2022 ◽  
Vol 5 (4) ◽  
pp. e202101315
Author(s):  
Stefanie Dichtl ◽  
David E Sanin ◽  
Carolin K Koss ◽  
Sebastian Willenborg ◽  
Andreas Petzold ◽  
...  

Anti-TNF therapies are a core anti-inflammatory approach for chronic diseases such as rheumatoid arthritis and Crohn’s Disease. Previously, we and others found that TNF blocks the emergence and function of alternative-activated or M2 macrophages involved in wound healing and tissue-reparative functions. Conceivably, anti-TNF drugs could mediate their protective effects in part by an altered balance of macrophage activity. To understand the mechanistic basis of how TNF regulates tissue-reparative macrophages, we used RNAseq, scRNAseq, ATACseq, time-resolved phospho-proteomics, gene-specific approaches, metabolic analysis, and signaling pathway deconvolution. We found that TNF controls tissue-reparative macrophage gene expression in a highly gene-specific way, dependent on JNK signaling via the type 1 TNF receptor on specific populations of alternative-activated macrophages. We further determined that JNK signaling has a profound and broad effect on activated macrophage gene expression. Our findings suggest that TNF’s anti-M2 effects evolved to specifically modulate components of tissue and reparative M2 macrophages and TNF is therefore a context-specific modulator of M2 macrophages rather than a pan-M2 inhibitor.


2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Ki Hyun Nam

AbstractSerial crystallography (SX) enables the visualization of the time-resolved molecular dynamics of macromolecular structures at room temperature while minimizing radiation damage. In SX experiments, the delivery of a large number of crystals into an X-ray interaction point in a serial and stable manner is key. Sample delivery using viscous medium maintains the stable injection stream at low flow rates, markedly reducing sample consumption compared with that of a liquid jet injector and is widely applied in SX experiments with low repetition rates. As the sample properties and experimental environment can affect the stability of the injection stream of a viscous medium, it is important to develop sample delivery media with various characteristics to optimize the experimental environment. In this study, a beef tallow injection matrix possessing a higher melting temperature than previously reported fat-based shortening and lard media was introduced as a sample delivery medium and applied to SX. Beef tallow was prepared by heat treating fats from cattle, followed by the removal of soluble impurities from the extract by phase separation. Beef tallow exhibited a very stable injection stream at room temperature and a flow rate of < 10 nL/min. The room-temperature structures of lysozyme and glucose isomerase embedded in beef tallow were successfully determined at 1.55 and 1.60 Å, respectively. The background scattering of beef tallow was higher than that of previously reported fat-based shortening and lard media but negligible for data processing. In conclusion, the beef tallow matrix can be employed for sample delivery in SX experiments conducted at temperatures exceeding room temperature.


Crystals ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 99
Author(s):  
Ki Hyun Nam

Serial crystallography (SX) is an emerging technique to determine macromolecules at room temperature. SX with a pump–probe experiment provides the time-resolved dynamics of target molecules. SX has developed rapidly over the past decade as a technique that not only provides room-temperature structures with biomolecules, but also has the ability to time-resolve their molecular dynamics. The serial femtosecond crystallography (SFX) technique using an X-ray free electron laser (XFEL) has now been extended to serial synchrotron crystallography (SSX) using synchrotron X-rays. The development of a variety of sample delivery techniques and data processing programs is currently accelerating SX research, thereby increasing the research scope. In this editorial, I briefly review some of the experimental techniques that have contributed to advances in the field of SX research and recent major research achievements. This Special Issue will contribute to the field of SX research.


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