Restriction endonuclease BpuJI specific for the 5′-CCCGT sequence is related to the archaeal Holliday junction resolvase family

Type IIS restriction endonucleases (REases) recognize asymmetric DNA sequences and cleave both DNA strands at fixed positions downstream of the recognition site. REase BpuJI recognizes the asymmetric sequence 5′-CCCGT, however it cuts at multiple sites in the vicinity of the target sequence. We show that BpuJI is a dimer, which has two DNA binding surfaces and displays optimal catalytic activity when bound to two recognition sites. BpuJI is cleaved by chymotrypsin into an N-terminal domain (NTD), which lacks catalytic activity but binds specifically to the recognition sequence as a monomer, and a C-terminal domain (CTD), which forms a dimer with non-specific nuclease activity. Fold recognition approach reveals that the CTD of BpuJI is structurally related to archaeal Holliday junction resolvases (AHJR). We demonstrate that the isolated catalytic CTD of BpuJI possesses end-directed nuclease activity and preferentially cuts 3 nt from the 3′-terminus of blunt-ended DNA. The nuclease activity of the CTD is repressed in the apo-enzyme and becomes activated upon specific DNA binding by the NTDs. This leads to a complicated pattern of specific DNA cleavage in the vicinity of the target site. Bioinformatics analysis identifies the AHJR-like domain in the putative Type III enzymes and functionally uncharacterized proteins

Challenges in QCD matter physics - The Compressed Baryonic Matter experiment at FAIR

Substantial experimental and theoretical efforts worldwide are devoted to explore the phase diagram of strongly interacting matter. At LHC and top RHIC energies, QCD matter is studied at very high temperatures and nearly vanishing net-baryon densities. There is evidence that a Quark-Gluon-Plasma (QGP) was created at experiments at RHIC and LHC. The transition from the QGP back to the hadron gas is found to be a smooth cross over. For larger net-baryon densities and lower temperatures, it is expected that the QCD phase diagram exhibits a rich structure, such as a first-order phase transition between hadronic and partonic matter which terminates in a critical point, or exotic phases like quarkyonic matter. The discovery of these landmarks would be a breakthrough in our understanding of the strong interaction and is therefore in the focus of various high-energy heavy-ion research programs. The Compressed Baryonic Matter (CBM) experiment at FAIR will play a unique role in the exploration of the QCD phase diagram in the region of high net-baryon densities, because it is designed to run at unprecedented interaction rates. High-rate operation is the key prerequisite for high-precision measurements of multi-differential observables and of rare diagnostic probes which are sensitive to the dense phase of the nuclear fireball. The goal of the CBM experiment at SIS100 (sqrt(s_NN) = 2.7 - 4.9 GeV) is to discover fundamental properties of QCD matter: the phase structure at large baryon-chemical potentials (mu_B > 500 MeV), effects of chiral symmetry, and the equation-of-state at high density as it is expected to occur in the core of neutron stars. In this article, we review the motivation for and the physics programme of CBM, including activities before the start of data taking in 2022, in the context of the worldwide efforts to explore high-density QCD matter.Comment: 15 pages, 11 figures. Published in European Physical Journal

Structural basis of envelope and phase intrinsic coupling modes in the cerebral cortex

Intrinsic coupling modes (ICMs) can be observed in ongoing brain activity at multiple spatial and temporal scales. Two families of ICMs can be distinguished: phase and envelope ICMs. The principles that shape these ICMs remain partly elusive, in particular their relation to the underlying brain structure. Here we explored structure-function relationships in the ferret brain between ICMs quantified from ongoing brain activity recorded with chronically implanted micro-ECoG arrays and structural connectivity (SC) obtained from high-resolution diffusion MRI tractography. Large-scale computational models were used to explore the ability to predict both types of ICMs. Importantly, all investigations were conducted with ICM measures that are sensitive or insensitive to volume conduction effects. The results show that both types of ICMs are significantly related to SC, except for phase ICMs when using measures removing zero-lag coupling. The correlation between SC and ICMs increases with increasing frequency which is accompanied by reduced delays. Computational models produced results that were highly dependent on the specific parameter settings. The most consistent predictions were derived from measures solely based on SC. Overall, the results demonstrate that patterns of cortical functional coupling as reflected in both phase and envelope ICMs are both related, albeit to different degrees, to the underlying structural connectivity in the cerebral cortex.This work was supported by funding from the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) - SFB 936 - 178316478 - A1 (C.C.H.), A2 (A.K.E.), and Z3 (C.C.H. and A.M.), SPP1665 - 220176618 - EN533/13-1 (A.K.E.), SPP2041 - 313856816 - HI1286/6-1 (C.C.H.) and EN533/15-1 (A.K.E.), from the European Unions Horizon 2020 Framework Programme for Research and Innovation under Specific Grant Agreements 785907 and 945539 (Human Brain Project SGA2 and SGA3, C.C.H.), and from the 2015 FLAG-ERA Joint Transnational Call for project FIIND - ANR-15-HBPR-0005 (R.T.).Peer reviewe

Effect of tiotropium on COPD exacerbations: A systematic review

Exacerbation frequency is related to disease progression, quality of life, and prognosis in COPD. Earlier diagnosis, along with interventions aimed at preventing exacerbations and delaying progression, may help reduce the global burden of disease. Long-acting inhaled bronchodilators are effective at maintaining symptom relief and are recommended as first-choice therapy for more symptomatic patients and those at risk of exacerbation.This article is freely available via Open Access. Click on the 'Additional Link' above to access the full-text from the publisher's site.Published (Open Access

Cause of Death and Predictors of All-Cause Mortality in Anticoagulated Patients With Nonvalvular Atrial Fibrillation : Data From ROCKET AF

M. Kaste on työryhmän ROCKET AF Steering Comm jäsen.Background-Atrial fibrillation is associated with higher mortality. Identification of causes of death and contemporary risk factors for all-cause mortality may guide interventions. Methods and Results-In the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) study, patients with nonvalvular atrial fibrillation were randomized to rivaroxaban or dose-adjusted warfarin. Cox proportional hazards regression with backward elimination identified factors at randomization that were independently associated with all-cause mortality in the 14 171 participants in the intention-to-treat population. The median age was 73 years, and the mean CHADS(2) score was 3.5. Over 1.9 years of median follow-up, 1214 (8.6%) patients died. Kaplan-Meier mortality rates were 4.2% at 1 year and 8.9% at 2 years. The majority of classified deaths (1081) were cardiovascular (72%), whereas only 6% were nonhemorrhagic stroke or systemic embolism. No significant difference in all-cause mortality was observed between the rivaroxaban and warfarin arms (P=0.15). Heart failure (hazard ratio 1.51, 95% CI 1.33-1.70, P= 75 years (hazard ratio 1.69, 95% CI 1.51-1.90, P Conclusions-In a large population of patients anticoagulated for nonvalvular atrial fibrillation, approximate to 7 in 10 deaths were cardiovascular, whereasPeer reviewe

Problem der Fremdenverkehrsentwicklung in der Provinz Lecce, Puglia: Versuch e. Vergleichs mit e. bereits entwickelten Region

Available from Bibliothek des Instituts fuer Weltwirtschaft, ZBW, Duesternbrook Weg 120, D-24105 Kiel A 171114 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman

Lymphatic System and Fistulas—Radiological Imaging Primer

While the imaging of arteries and veins by CT, MRI, and angiography is standard practice in large and small hospitals as well as in outpatient practices in developed countries, the diverse and sophisticated radiological procedures for imaging lymph ducts are often unknown and available only in a few specialized institutions [...

Unusual Left Periclavicular Cutaneous Lymphatic Fistula After Port Explantation Without Lymph Vessel Injury: Imaging and Interventional Treatment

Complex oncological treatment can be associated with lymphatic vascular injury that is burdened by considerable morbidity. Lymphatic imaging and interventional techniques offer new minimally invasive treatment options. We report the case of a 59-year-old woman with an unusual lympho-veno-cutaneous fistula, diagnosed by magnetic resonance lymphangiography and treated by minimally invasive embolization therapy and venous recanalization