Microstructural Parcellation of the Human Cerebral Cortex – From Brodmann's Post-Mortem Map to in vivo Mapping with High-Field Magnetic Resonance Imaging

The year 2009 marked the 100th anniversary of the publication of the famous brain map of Korbinian Brodmann. Although a “classic” guide to microanatomical parcellation of the cerebral cortex, it is – from today's state-of-the-art neuroimaging perspective – problematic to use Brodmann's map as a structural guide to functional units in the cortex. In this article we discuss some of the reasons, especially the problematic compatibility of the “post-mortem world” of microstructural brain maps with the “in vivo world” of neuroimaging. We conclude with some prospects for the future of in vivo structural brain mapping: a new approach which has the enormous potential to make direct correlations between microstructure and function in living human brains: “in vivo Brodmann mapping” with high-field magnetic resonance imaging

Selective photodissociation of tailored molecular tags as a tool for quantum optics

Recent progress in synthetic chemistry and molecular quantum optics has enabled demonstrations of the quantum mechanical wave–particle duality for complex particles, with masses exceeding 10 kDa. Future experiments with even larger objects will require new optical preparation and manipulation methods that shall profit from the possibility to cleave a well-defined molecular tag from a larger parent molecule. Here we present the design and synthesis of two model compounds as well as evidence for the photoinduced beam depletion in high vacuum in one case

Pushing the mass limit for intact launch and photoionization of large neutral biopolymers

Since their first discovery by Louis Dunoyer and Otto Stern, molecular beams have conquered research and technology. However, it has remained an outstanding challenge to isolate and photoionize beams of massive neutral polypeptides. Here we show that femtosecond desorption from a matrix-free sample in high vacuum can produce biomolecular beams at least 25 times more efficiently than nanosecond techniques. While it has also been difficult to photoionize large biomolecules, we find that tailored structures with an abundant exposure of tryptophan residues at their surface can be ionized by vacuum ultraviolet light. The combination of these desorption and ionization techniques allows us to observe molecular beams of neutral polypeptides with a mass exceeding 20,000 amu. They are composed of 50 amino acids – 25 tryptophan and 25 lysine residues – and 26 fluorinated alkyl chains. The tools presented here offer a basis for the preparation, control and detection of polypeptide beams

Isotope-selective high-order interferometry with large organic molecules in free fall

Interferometry in the time domain has proven valuable for matter-wave based measurements. This concept has recently been generalized to cold molecular clusters using short-pulse standing light waves which realized photo-depletion gratings, arranged in a time-domain TalbotâEuro"Lau interferometer (OTIMA). Here we extend this idea further to large organic molecules and demonstrate a new scheme to scan the emerging molecular interferogram in position space. The capability of analyzing different isotopes of the same monomer under identical conditions opens perspectives for studying the interference fringe shift as a function of time in gravitational free fall. The universality of OTIMA interferometry allows one to handle a large variety of particles. In our present work, quasi-continuous laser evaporation allows transferring fragile organic molecules into the gas phase, covering more than an order of magnitude in mass between 614 amu and 6509 amu, i.e. 300% more massive than in previous OTIMA experiments. For all masses, we find about 30% fringe visibility

Neutralization of insulin by photocleavage under high vacuum

Charge reduction and neutralization of electro-sprayed peptides are realized by selective gas-phase photocleavage of tailored covalent tags. The concept is demonstrated with four model peptides in positive and negative ion modes and tagged insulin as the largest construct

Antiviral signaling by a cyclic nucleotide activated CRISPR protease

Funding information: M.G. and J.L.S.B. are funded by the Deutsche Forschungsgemeinschaft under Germany’s Excellence Strategy–EXC2151–390873048. M.F.W. acknowledges a European Research Council Advanced Grant (grant number 101018608) and the China Scholarship Council (REF: 202008420207 to H.C.). G.H. is grateful for funding by the Deutsche Forschungsgemeinschaft (grant number HA6805/6-1).CRISPR defense systems such as the well-known DNA-targeting Cas9 and the RNA-targeting type III systems are widespread in prokaryotes1,2. The latter can orchestrate a complex antiviral response that is initiated by the synthesis of cyclic oligoadenylates (cOAs) upon foreign RNA recognition3-5. Among a large set of proteins that were linked to type III systems and predicted to bind cOAs6,7, a CRISPR associated Lon protease (CalpL) stood out to us. The protein contains a sensor domain of the SAVED (SMODS-associated and fused to various effector domains) family7, fused to a Lon protease effector domain. However, the mode of action of this effector was unknown. Here, we report the structure and function of CalpL and show that the soluble protein forms a stable tripartite complex with two further proteins, CalpT and CalpS, that are encoded in the same operon. Upon activation by cA4, CalpL oligomerizes and specifically cleaves the MazF-homolog CalpT, releasing the extracytoplasmic function (ECF) sigma factor CalpS from the complex. This provides a direct connection between CRISPR-based foreign nucleic acid detection and transcriptional regulation. Furthermore, the presence of a cA4-binding SAVED domain in a CRISPR effector reveals an unexpected link to the cyclic oligonucleotide-based antiphage signaling system (CBASS).PostprintPeer reviewe

Acoustic cardiac triggering: a practical solution for synchronization and gating of cardiovascular magnetic resonance at 7 Tesla

<p>Abstract</p> <p>Background</p> <p>To demonstrate the applicability of acoustic cardiac triggering (ACT) for imaging of the heart at ultrahigh magnetic fields (7.0 T) by comparing phonocardiogram, conventional vector electrocardiogram (ECG) and traditional pulse oximetry (POX) triggered 2D CINE acquisitions together with (i) a qualitative image quality analysis, (ii) an assessment of the left ventricular function parameter and (iii) an examination of trigger reliability and trigger detection variance derived from the signal waveforms.</p> <p>Results</p> <p>ECG was susceptible to severe distortions at 7.0 T. POX and ACT provided waveforms free of interferences from electromagnetic fields or from magneto-hydrodynamic effects. Frequent R-wave mis-registration occurred in ECG-triggered acquisitions with a failure rate of up to 30% resulting in cardiac motion induced artifacts. ACT and POX triggering produced images free of cardiac motion artefacts. ECG showed a severe jitter in the R-wave detection. POX also showed a trigger jitter of approximately Δt = 72 ms which is equivalent to two cardiac phases. ACT showed a jitter of approximately Δt = 5 ms only. ECG waveforms revealed a standard deviation for the cardiac trigger offset larger than that observed for ACT or POX waveforms.</p> <p>Image quality assessment showed that ACT substantially improved image quality as compared to ECG (image quality score at end-diastole: ECG = 1.7 ± 0.5, ACT = 2.4 ± 0.5, p = 0.04) while the comparison between ECG vs. POX gated acquisitions showed no significant differences in image quality (image quality score: ECG = 1.7 ± 0.5, POX = 2.0 ± 0.5, p = 0.34).</p> <p>Conclusions</p> <p>The applicability of acoustic triggering for cardiac CINE imaging at 7.0 T was demonstrated. ACT's trigger reliability and fidelity are superior to that of ECG and POX. ACT promises to be beneficial for cardiovascular magnetic resonance at ultra-high field strengths including 7.0 T.</p