The atypical mammalian ligand Delta-like homologue 1 (Dlk1) can regulate Notch signalling in Drosophila

<p>Abstract</p> <p>Background</p> <p>Mammalian <it>Delta-like 1 </it>(<it>Dlk-1</it>) protein shares homology with Notch ligands but lacks a critical receptor-binding domain. Thus it is unclear whether it is able to interact with Notch <it>in vivo</it>. Unlike mammals, <it>Drosophila </it>have a single Notch receptor allowing a simple <it>in vivo </it>assay for mammalian <it>Dlk1 </it>function.</p> <p>Results</p> <p>Here we show that membrane-bound DLK1 can regulate Notch leading to altered cellular distribution of Notch itself and inhibiting expression of Notch target genes. The resulting adult phenotypes are indicative of reduced Notch function and are enhanced by <it>Notch </it>mutations, confirming that DLK1 action is antagonistic. In addition, cells expressing an alternative <it>Dlk1 </it>isoform exhibit alterations in cell size, functions previously not attributed to Notch suggesting that DLK1 might also act via an alternative target.</p> <p>Conclusion</p> <p>Our results demonstrate that DLK1 can regulate the Notch receptor despite its atypical structure.</p

Active Initialization Experiment of Superconducting Qubit Using Quantum-circuit Refrigerator

The initialization of superconducting qubits is one of the essential techniques for the realization of quantum computation. In previous research, initialization above 99\% fidelity has been achieved at 280 ns. Here, we demonstrate the rapid initialization of a superconducting qubit with a quantum-circuit refrigerator (QCR). Photon-assisted tunneling of quasiparticles in the QCR can temporally increase the relaxation time of photons inside the resonator and helps release energy from the qubit to the environment. Experiments using this protocol have shown that 99\% of initialization time is reduced to 180 ns. This initialization time depends strongly on the relaxation rate of the resonator, and faster initialization is possible by reducing the resistance of the QCR, which limits the ON/OFF ratio, and by strengthening the coupling between the QCR and the resonator

Management strategy for acute pancreatitis in the JPN Guidelines

The diagnosis of acute pancreatitis is based on the following findings: (1) acute attacks of abdominal pain and tenderness in the epigastric region, (2) elevated blood levels of pancreatic enzymes, and (3) abnormal diagnostic imaging findings in the pancreas associated with acute pancreatitis. In Japan, in accordance with criteria established by the Japanese Ministry of Health, Labour, and Welfare, the severity of acute pancreatitis is assessed based on the clinical signs, hematological findings, and imaging findings, including abdominal contrast-enhanced computed tomography (CT) and magnetic resonance imaging (MRI). Severity must be re-evaluated, especially in the period 24 to 48 h after the onset of acute pancreatitis, because even cases diagnosed as mild or moderate in the early stage may rapidly progress to severe. Management is selected according to the severity of acute pancreatitis, but it is imperative that an adequate infusion volume, vital-sign monitoring, and pain relief be instituted immediately after diagnosis in every patient. Patients with severe cases are treated with broad-spectrum antimicrobial agents, a continuous high-dose protease inhibitor, and continuous intraarterial infusion of protease inhibitors and antimicrobial agents; continuous hemodiafiltration may also be used to manage patients with severe cases. Whenever possible, transjejunal enteral nutrition should be administered, even in patients with severe cases, because it seems to decrease morbidity. Necrosectomy is performed when necrotizing pancreatitis is complicated by infection. In this case, continuous closed lavage or open drainage (planned necrosectomy) should be the selected procedure. Pancreatic abscesses are treated by surgical or percutaneous drainage. Emergency endoscopic procedures are given priority over other methods of management in patients with acute gallstone-associated pancreatitis, patients suspected of having bile duct obstruction, and patients with acute gallstone pancreatitis complicated by cholangitis. These strategies for the management of acute pancreatitis are shown in the algorithm in this article

Generation of a single-cycle acoustic pulse: a scalable solution for transport in single-electron circuits

The synthesis of single-cycle, compressed optical and microwave pulses sparked novel areas of fundamental research. In the field of acoustics, however, such a generation has not been introduced yet. For numerous applications, the large spatial extent of surface acoustic waves (SAW) causes unwanted perturbations and limits the accuracy of physical manipulations. Particularly, this restriction applies to SAW-driven quantum experiments with single flying electrons, where extra modulation renders the exact position of the transported electron ambiguous and leads to undesired spin mixing. Here, we address this challenge by demonstrating single-shot chirp synthesis of a strongly compressed acoustic pulse. Employing this solitary SAW pulse to transport a single electron between distant quantum dots with an efficiency exceeding 99%, we show that chirp synthesis is competitive with regular transduction approaches. Performing a time-resolved investigation of the SAW-driven sending process, we outline the potential of the chirped SAW pulse to synchronize single-electron transport from many quantum-dot sources. By superimposing multiple pulses, we further point out the capability of chirp synthesis to generate arbitrary acoustic waveforms tailorable to a variety of (opto)nanomechanical applications. Our results shift the paradigm of compressed pulses to the field of acoustic phonons and pave the way for a SAW-driven platform of single-electron transport that is precise, synchronized, and scalable.Comment: To be published in Physical Review

Loss of NSD2 causes dysregulation of synaptic genes and altered H3K36 dimethylation in mice

Background: Epigenetic disruptions have been implicated in neurodevelopmental disorders. NSD2 is associated with developmental delay/intellectual disability; however, its role in brain development and function remains unclear.Methods: We performed transcriptomic and epigenetic analyses using Nsd2 knockout mice to better understand the role of NSD2 in the brain.Results and discussion: Transcriptomic analysis revealed that the loss of NSD2 caused dysregulation of genes related to synaptic transmission and formation. By analyzing changes in H3 lysine 36 dimethylation (H3K36me2), NSD2-mediated H3K36me2 mainly marked quiescent state regions and the redistribution of H3K36me2 occurred at transcribed genes and enhancers. By integrating transcriptomic and epigenetic data, we observed that H3K36me2 changes in a subset of dysregulated genes related to synaptic transmission and formation. These results suggest that NSD2 is involved in the regulation of genes important for neural function through H3K36me2. Our findings provide insights into the role of NSD2 and improve our understanding of epigenetic regulation in the brain

Calaxin is required for cilia-driven determination of vertebrate laterality

Sasaki, K., Shiba, K., Nakamura, A. et al. Calaxin is required for cilia-driven determination of vertebrate laterality. Commun Biol 2, 226 (2019). https://doi.org/10.1038/s42003-019-0462-