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

Ligand-Specific Dynamics of the Androgen Receptor at Its Response Element in Living Cells

Androgens have key roles in normal physiology and in male sexual differentiation as well as in pathological conditions such as prostate cancer. Androgens act through the androgen receptor (AR), which is a ligand-modulated transcription factor. Antiandrogens block AR function and are widely used in disease states, but little is known about their mechanism of action in vivo. Here, we describe a rapid differential interaction of AR with target genomic sites in living cells in the presence of agonists which coincides with the recruitment of BRM ATPase complex and chromatin remodeling, resulting in transcriptional activation. In contrast, the interaction of antagonist-bound or mutant AR with its target was found to be kinetically different: it was dramatically faster, occurred without chromatin remodeling, and resulted in the lack of transcriptional inhibition. Fluorescent resonance energy transfer analysis of wild-type AR and a transcriptionally compromised mutant at the hormone response element showed that intramolecular interactions between the N and C termini of AR play a key functional role in vivo compared to intermolecular interactions between two neighboring ARs. These data provide a kinetic and mechanistic basis for regulation of gene expression by androgens and antiandrogens in living cells

Large plexiform neurofibroma on right thigh of a farmer in the course of Recklinghausen disease - Case report

A 59-year-old farmer was admitted to the Department of Trauma Surgery because of pain associated with the presence of a tumour on the side of the right thigh. The patient stated that his biggest problem was great difficulty in moving and handling agricultural machinery due to the aforementioned lesion. On physical examination, the patient presented with numerous cutaneous and subcutaneous neurofibromas, as well as one large plexiform neurofibroma. Diagnosis of Neurofibromatosis type 1 was established, based on National Institutes of Health diagnostic criteria. Moreover, molecular genetic testing found known pathogenic mutation p.Arg1769* in one of the alleles of NF1 gene (heterozygote), typical for Recklinghausen disease. The big plexiform neurofibroma in the patient was not operated on because of lung cancer