Domain Organization of Long Signal Peptides of Single-Pass Integral Membrane Proteins Reveals Multiple Functional Capacity

Targeting signals direct proteins to their extra - or intracellular destination such as the plasma membrane or cellular organelles. Here we investigated the structure and function of exceptionally long signal peptides encompassing at least 40 amino acid residues. We discovered a two-domain organization (“NtraC model”) in many long signals from vertebrate precursor proteins. Accordingly, long signal peptides may contain an N-terminal domain (N-domain) and a C-terminal domain (C-domain) with different signal or targeting capabilities, separable by a presumably turn-rich transition area (tra). Individual domain functions were probed by cellular targeting experiments with fusion proteins containing parts of the long signal peptide of human membrane protein shrew-1 and secreted alkaline phosphatase as a reporter protein. As predicted, the N-domain of the fusion protein alone was shown to act as a mitochondrial targeting signal, whereas the C-domain alone functions as an export signal. Selective disruption of the transition area in the signal peptide impairs the export efficiency of the reporter protein. Altogether, the results of cellular targeting studies provide a proof-of-principle for our NtraC model and highlight the particular functional importance of the predicted transition area, which critically affects the rate of protein export. In conclusion, the NtraC approach enables the systematic detection and prediction of cryptic targeting signals present in one coherent sequence, and provides a structurally motivated basis for decoding the functional complexity of long protein targeting signals

Pictorial review of COVID-19 in the Lublin Region – Imaging disease progression with CXR and CT

Introduction. COVID-19 is a disease caused by SARS-Cov-2 that has reached the pandemic status and has infected in one year more than 62 million people. Clinical symptoms range from barely noticeable to very severe. It is crucial to recognize imaging patterns of COVID-19, allowing for better diagnosis and treatment. Diagnostic imaging is also essential in monitoring patients in the course of the disease. Objective. In our pictorial review we describe the most common pulmonary manifestations of COVID-19, and show the typical and non-typical features of COVID-19 encountered in our hospital in Lublin, Poland. Imaging the disease progression is also visualized to help realize how pulmonary changes occur over the time. State of knowledge and Conclusions. COVID-19 involves both lung parenchyma and interstitium and has multiple imaging features, varying form ground glass opacities (GGO), consolidations, reticular interstitial pattern, honeycombing or crazy- paving. Mediastinal and hilar lymph node enlargement or pleural effusion may appear, but are rare and atypical. GGO are located peripherally, bilaterally and predominantly in the lower lobes, and in the early stage are better seen on CT imaging. Progression of imaging findings take different times, with the peak of of imaging features appearing around 10–14 days after initial symptoms. While it is harder to discern subtle changes on CXR, progression can be very well monitored by his method. Final pulmonary consequences of the disease should be assessed with the use of CT

Acute ischemic stroke within the area of MCA from ICA thrombosis complicating moderate COVID-19 infection

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome-coronavirus type 2 (SARS-Cov-2), injures multiple organs including the central and peripheral nervous system. We report the case of a 68-year-old patient diagnosed with COVID-19 infection in its moderate form who, 1 week after the onset of respiratory symptoms, developed a large acute ischemic stroke (AIS) in the area of the left middle cerebral artery (LMCA). The case shows that large artery stroke can occur even in moderate forms of COVID-19, and stresses the need for correct coagulation management. The source of cerebral stroke should also be sought by cervical computed tomography angiography (CTA) from the level of the aortic arch, and not only covering the cerebral vessels as thrombo-embolic events may appear already in large cervical vessels, even in mild forms of the disease