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Genome-scale metabolism custom modeling rendering discloses SARS-CoV-2-induced metabolic alterations as well as antiviral objectives.
Nostoc sp. PCC 7120 are filamentous cyanobacteria capable of both oxygenic photosynthesis and nitrogen fixation, with the latter taking place in specialized cells known as heterocysts that terminally differentiate from vegetative cells under conditions of nitrogen starvation. Cyanobacteria have existed on earth for more than 2 billion years and are thought to be responsible for oxygenation of the earth's atmosphere. Filamentous cyanobacteria such as Nostoc sp. PCC 7120 may also represent the oldest multicellular organisms on earth that undergo cell differentiation. Pentapeptide repeat proteins (PRPs), which occur most abundantly in cyanobacteria, adopt a right-handed quadrilateral β-helical structure, also referred to as a repeat five residue (Rfr) fold, with four-consecutive pentapeptide repeats constituting a single coil in the β-helical structure. PRPs are predicted to exist in all compartments within cyanobacteria including the thylakoid and cell-wall membranes as well as the cytoplasm and thylakoid periplasmic space. Despite their intriguing structure and importance to understanding ancient cyanobacteria, the biochemical function of PRPs in cyanobacteria remains largely unknown. Here we report the crystal structure of Alr1298, a PRP from Nostoc sp. PCC 7120 predicted to reside in the cytoplasm. The structure displays the typical right-handed quadrilateral β-helical structure and includes a four-α-helix cluster capping the N-terminus and a single α-helix capping the C-terminus. A gene cluster analysis indicated that Alr1298 may belong to an operon linked to cell proliferation and/or thylakoid biogenesis. Elevated alr1298 gene expression following nitrogen starvation indicates that Alr1298 may play a role in response to nitrogen starvation and/or heterocyst differentiation. © 2020 Wiley Periodicals, Inc.Polydopamine (PD) and melanin species are chemically complex systems whose formation and properties are incompletely understood. Inspired by the role of functional amyloids in melanin biosynthesis, this paper examines influences of amyloid supramolecular structures on oxidation polymerization of dopamine. Kinetic analyses on the formation of PD species in the presence of Hen Egg White Lysozyme (HEWL) fibers or soluble HEWL revealed that the both forms gave rise to the total quantity of PD species, but the rate of their formation could be accelerated only by the amyloid form. PD species formed with HEWL fibers showed a morphology of bundled fibers, whereas those with soluble HEWL had a mesh-like structure. Amyloid fibers of recombinant Pmel17 had a similar property with HEWL fibers in modulating PD formation. The results presented here suggests a way how nature designs functionality with an amyloid structure and would help understand or engineer chemistries of other functional amyloids. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.NEW FINDINGS What is the topic of this review? This review concerns the negative impact of pulmonary hypertension (PH) on the pulmonary haemodynamic and gas exchange responses to exercise, considering the mechanisms by which PH plays a role in exercise intolerance in heart failure (HF) patients. What advances does it highlight? The hallmark limited pulmonary vascular 'reserve' and impaired pulmonary gas exchange responses to exercise in HF are worsened by the development of PH; these are key determinants of exercise intolerance. Even HF patients who present with 'normal' pulmonary vascular function experience exercise-induced PH, which plays a role in exercise intolerance. ABSTRACT Patients with heart failure universally complain of exertional intolerance, but the underlying cause(s) of this intolerance may differ between patients with different disease phenotypes. Trichostatin A in vitro Exercise introduces an impressive stress to the lungs, where elevations in venous return and cardiac output engender substantial increases in pulmasures of exercise pulmonary gas exchange might help to 'describe' underlying PH in heart failure; however, several fundamental issues and questions need to be addressed before such gas exchange measures could truly be considered efficacious measures used to differentiate the type of PH and track the severity of PH in heart failure. exercise intolerance, heart failure, pulmonary gas exchange, pulmonary haemodynamics, pulmonary hypertension. © 2020 The Authors. Experimental Physiology © 2020 The Physiological Society.in German This work describes the first example of Michael addition reactions of chiral Ni (II)-complex of glycine Schiff base with 1-(1-(phenylsulfonyl)vinylsulfonyl)benzene. This approach was developed for asymmetric synthesis of 2-amino-4,4-bis (phenylsulfonyl)butanoic acid possessing various design-useful properties such as substantial steric bulk and lipophilicity. These properties are expected to provide for an improved binding to the apolar site of the various endogenous receptors. Fmoc derivative of the target amino acids ready for peptide coupling is described.OBJECTIVE We aim to evaluate the midterm effect of chronic apical right ventricular (RV) pacing on right and left ventricular (LV) function using different modalities of echocardiography including conventional echocardiography, tissue Doppler imaging and two-dimension speckle tracking echocardiography. METHODS This case-control study enrolled 49 patients divided into two groups a paced group and a nonpaced group. The paced group included 23 patients that underwent tetralogy of Fallot (TOF) repair and required permanent pacemaker insertion for postoperative complete heart block. The nonpaced group included 26 patients that had TOF repair at the same period. RESULTS The median age for the paced and nonpaced groups was 6 and 8 years, respectively (P = .169). The follow-up duration after TOF surgical repair was 4 years for the paced patients and 5 years for nonpaced patients (P = .411). In the nonpaced group, the QRS duration increased and LV global longitudinal strain (GLS) decreased significantly with increasing duration after TOF repair, P value was .006 and .042, respectively. In the paced group, tricuspid annular systolic plane excursion (TAPSE) was significantly correlated with age (r = .578; P = .004) and duration following TOF correction (r = .724; P  less then  .001). CONCLUSION Chronic RV apical pacing in children after TOF repair was associated with better clinical status, preservation of RV systolic function, and prevention of progressive QRS prolongation. RV pacing was not associated with progressive deterioration of LV systolic function with increasing the time interval following TOF repair. Therefore, RV pacing can be beneficial in corrected TOF patients presenting with RV failure. © 2020 Wiley Periodicals, Inc.The reactions of the monomeric C,N-chelated organogermanium(II) hydride L(H)Ge·BH3 with organolithium salts RLi yielded lithium hydrogermanatoborates Li(THF)2BH3[L(H)GeR]2. Compound Li(THF)2BH3[L(H)GePh]2 was used as a source of LiH for the reduction of organic C=O or C=N bonds in non-polar solvents accompanied by the elimination of a neutral complex L(Ph)Ge·BH3. The interaction of Li(THF)2BH3[L(H)GePh]2 with the C=O polar bond was further investigated by computational studies revealing a plausible geometry of a pre-reactive intermediate. The experimental and theoretical studies suggest that while the Li atom of Li(THF)2BH3[L(H)GePh] coordinates the C=O bond, the GeH fragment is the active species in the reduction reaction. Finally, benzaldehyde was reduced by the mixture of L(H)Ge·BH3 with PhLi in non-polar solvents. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.BACKGROUND Access to centers with extracorporeal membrane oxygenation (ECMO) capabilities varies by region and may affect overall outcomes. We assessed the outcomes of trauma patients requiring ECMO support and compared the overall survival of all patients with trauma at facilities with and without ECMO capabilities. METHODS A retrospective review of the National Trauma Data Bank was performed to identify all trauma patients receiving care at ECMO and non-ECMO centers. Baseline patient characteristics and outcomes were analyzed. Adjusted odds ratio (OR) was used to compare survival at ECMO and non-ECMO facilities. RESULTS Between 2007 and 2015, a total of 5 781 123 patients with trauma were identified with 1 983 986 (34%) admitted to an ECMO facility and 3 797 137 (66%) admitted to a non-ECMO facility. A total of 522 (0.03%) patients required ECMO. Both the number of patients with trauma requiring ECMO support and the number of trauma facilities utilizing ECMO increased over the 9-year-study period (4.9 to 13.8 patients per 100 000 admissions, and 18 to 77 centers, respectively). The mortality for ECMO patients was 40.5%. Patients with trauma admitted to ECMO facilities had more severe injuries (injury severity score 9.0 vs 8.0; P  less then  .001). The overall mortality was 3.3%. The adjusted OR for mortality associated with admission to an ECMO facility vs a non-ECMO facility was 0.96 (95% confidence interval 0.95-0.97; adjusted P  less then  .001). CONCLUSIONS The use of ECMO for patients with trauma is expanding. Our study demonstrates a survival benefit associated with admission to a facility with ECMO capabilities. Thus, access to ECMO is a potential quality metric for trauma centers. © 2020 Wiley Periodicals, Inc.BACKGROUND The Magnetic Resonance Parkinsonism Index is listed as one of the most reliable imaging morphometric markers for diagnosis of progressive supranuclear palsy (PSP). However, the use of this index in diagnostic workup has been limited until now by the low generalizability of published results because of small monocentric patient cohorts, the lack of data validation in independent patient series, and manual measurements used for index calculation. The objectives of this study were to investigate the generalizability of Magnetic Resonance Parkinsonism Index performance validating previously established cutoff values in a large international cohort of PSP patients subclassified into PSP-Richardson's syndrome and PSP-parkinsonism and to standardize the use of the automated Magnetic Resonance Parkinsonism Index by providing a web-based platform to obtain homogenous measures around the world. METHODS In a retrospective international multicenter study, a total of 173 PSP patients and 483 non-PSP participantonism Index to different clinical and research settings. © 2020 International Parkinson and Movement Disorder Society. © 2020 International Parkinson and Movement Disorder Society.BACKGROUND To create equitable access to donor organs for the highest mortality patients, the cardiac transplant allocation system now prioritizes patients with surgically implanted temporary left ventricular assist devices (T-LVADs). The outcomes following a direct bridge from a T-LVAD to orthotopic heart transplant (OHT) are not well delineated. AIM This study investigates the T-LVAD waitlist outcomes and compares the posttransplant outcomes in patients bridged to OHT with surgically implanted T-LVADs to patients bridged with durable continuous-flow left ventricular assist devices (CF-LVADs). METHODS Adults recorded in the United Network for Organ Sharing registry bridged to OHT with a durable CF-LVAD and T-LVADs, with or without temporary right ventricular assist devices (T-RVADs), between 2010 and 2018 were included. Propensity matching and multivariable Cox regression were utilized to compare outcomes. RESULTS Of 504 patients waitlisted with T-LVADs, the majority were transplanted (50%), bridged to CF-LVAD (17%), or recovered (9%).
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