Mechanisms by which G-patch activators tune the processive multi-tasking ATP-dependent RNA helicase Prp43 (DHX15 in humans) to productively remodel diverse RNA:protein complexes remain elusive. Here, a comparative study between a herein and previously characterized activators, Tma23 and Pxr1, respectively, defines segments that organize Prp43 function during ribosome assembly. In addition to the activating G-patch, we discover an inhibitory segment within Tma23 and Pxr1, I-patch, that restrains Prp43 ATPase activity.
View Article and Find Full Text PDFBackground: Despite its potential to improve patient access, streamline administration, and enhance healthcare efficiency, systematic data on online appointment scheduling (OAS) in medical practices is lacking.
Method: Prospective, single center study conducted at an ophthalmology practice. Over a period of 12 weeks, all booked appointments, both online made via the OAS system, and offline made by practice staff via phone, email, or in-person, were recorded across four doctor consultations.
Increasingly many studies reveal how ribosome composition can be tuned to optimally translate the transcriptome of individual cell types. In this study, we investigated the expression pattern, structure within the ribosome and effect on protein synthesis of the ribosomal protein paralog 39L (RPL39L). With a novel mass spectrometric approach we revealed the expression of RPL39L protein beyond mouse germ cells, in human pluripotent cells, cancer cell lines and tissue samples.
View Article and Find Full Text PDFThe pyruvate dehydrogenase complex (PDHc) is a key megaenzyme linking glycolysis with the citric acid cycle. In mammalian PDHc, dihydrolipoamide acetyltransferase (E2) and the dihydrolipoamide dehydrogenase-binding protein (E3BP) form a 60-subunit core that associates with the peripheral subunits pyruvate dehydrogenase (E1) and dihydrolipoamide dehydrogenase (E3). The structure and stoichiometry of the fully assembled, mammalian PDHc or its core remained elusive.
View Article and Find Full Text PDFPurpose: To describe optical coherence tomography angiography (OCTA)-guided navigated laser photocoagulation (LP) using the Navilas Laser System for treating retinal hemangioblastomas (RHs) associated with von Hippel-Lindau disease (VHLD).
Methods: Patients with VHLD were screened using ophthalmoscopy and widefield OCTA. Detected RHs were classified with regard to tumor morphology (endophytic, sessile, exophytic, recurrent) and size.
Amyloids are known as irreversible aggregates associated with neurodegenerative diseases. However, recent evidence shows that a subset of amyloids can form reversibly and fulfill essential cellular functions. Yet, the molecular mechanisms regulating functional amyloids and distinguishing them from pathological aggregates remain unclear.
View Article and Find Full Text PDFPhase transitions are important to understand cell dynamics, and the maturation of liquid droplets is relevant to neurodegenerative disorders. We combined NMR and Raman spectroscopies with microscopy to follow, over a period of days to months, droplet maturation of the protein fused in sarcoma (FUS). Our study reveals that the surface of the droplets plays a critical role in this process, while RNA binding prevents it.
View Article and Find Full Text PDFPurpose: To evaluate early detection of retinal hemangioblastomas (RHs) in von Hippel-Lindau disease (VHLD) with widefield optical coherence tomography angiography (wOCTA) compared to the standard of care in ophthalmologic VHLD screening in a routine clinical setting.
Methods: We conducted prospective comparisons of three screening methods: wOCTA, standard ophthalmoscopy, and fluorescein angiography (FA), which was performed only in uncertain cases. The numbers of detected RHs were compared among the three screening methods.
Purpose: Hypoxia-inducible factors (HIFs) are considered to play a significant role in the pathogenesis of pterygium. The aim of this study was to investigate the relative expression or immunoreactivity of HIF1α and HIF2α in the epithelium of primary pterygium, recurrences and healthy conjunctiva.
Methods: Immunohistochemical staining was performed with antibodies against HIF1α and HIF2α, respectively, on 55/84 primary pterygium specimens, 6/28 recurrences and 20/20 control tissues (healthy conjunctiva).
The discovery of nackednaviruses provided new insight into the evolutionary history of the hepatitis B virus (HBV): The common ancestor of HBV and nackednaviruses was non-enveloped and while HBV acquired an envelope during evolution, nackednaviruses remained non-enveloped. We report the capsid structure of the African cichlid nackednavirus (ACNDV), determined by cryo-EM at 3.7 Å resolution.
View Article and Find Full Text PDFPurpose: Single center study to evaluate the incidence and long-term outcome of laser pointer maculopathy (LPM).
Methods: Medical records of 909,150 patients visiting our institution between 2007 and 2020 were screened in our electronic patient record system using the keywords "laserpointer," "laser pointer," and "solar."
Results: Eight patients (6/2 male/female, 11 eyes) with a history of LPM were identified by fundoscopy and optical coherence tomography (OCT), all of whom were children (6/2 male/female).
Graefes Arch Clin Exp Ophthalmol
April 2023
Purpose: We herein compare topical interferon alpha 2b (IFN-α2b) to topical mitomycin C (MMC) in the adjuvant management after excision of primary acquired melanosis with atypia (PAM) and melanoma of the conjunctiva/cornea (CM).
Methods: We included 25 tumors from 25 patients (six with PAM and 19 with CM). After surgical excision, four patients started with adjuvant IFN-α2b (two in combination with radiotherapy), 19 with MMC, and two with radiotherapy alone.
Heterogenous nuclear ribonucleoproteins (hnRNPs) are abundant proteins implicated in various steps of RNA processing that assemble on nuclear RNA into larger complexes termed 40S hnRNP particles. Despite their initial discovery 55 years ago, our understanding of these intriguing macromolecular assemblies remains limited. Here, we report the biochemical purification of native 40S hnRNP particles and the determination of their complete protein composition by label-free quantitative mass spectrometry, identifying A-group and C-group hnRNPs as the major protein constituents.
View Article and Find Full Text PDFMitochondrial ribosomes (mitoribosomes) play a central role in synthesizing mitochondrial inner membrane proteins responsible for oxidative phosphorylation. Although mitoribosomes from different organisms exhibit considerable structural variations, recent insights into mitoribosome assembly suggest that mitoribosome maturation follows common principles and involves a number of conserved assembly factors. To investigate the steps involved in the assembly of the mitoribosomal small subunit (mt-SSU) we determined the cryoelectron microscopy structures of middle and late assembly intermediates of the mitochondrial small subunit (mt-SSU) at 3.
View Article and Find Full Text PDFBackground/aims: Surgical procedures in ophthalmology underlie variations over different time periods and are strongly dependent on the technical process and the invention of innovative surgical techniques. Especially, in glaucoma surgery a lot of surgical devices and techniques have been introduced during the last years. Until now, the use of these newer techniques has not been shown on a robust data basis.
View Article and Find Full Text PDFBiogenesis of ribosomal subunits involves enzymatic modifications of rRNA that fine-tune functionally important regions. The universally conserved prokaryotic dimethyltransferase KsgA sequentially modifies two universally conserved adenosine residues in helix 45 of the small ribosomal subunit rRNA, which is in proximity of the decoding site. Here we present the cryo-EM structure of Escherichia coli KsgA bound to an E.
View Article and Find Full Text PDFThe conserved signal recognition particle (SRP) cotranslationally delivers ~30% of the proteome to the eukaryotic endoplasmic reticulum (ER). The molecular mechanism by which eukaryotic SRP transitions from cargo recognition in the cytosol to protein translocation at the ER is not understood. Here, structural, biochemical, and single-molecule studies show that this transition requires multiple sequential conformational rearrangements in the targeting complex initiated by guanosine triphosphatase (GTPase)-driven compaction of the SRP receptor (SR).
View Article and Find Full Text PDFBackground/aims: Retinal haemangioblastomas (RH) remain a major cause of visual impairment in patients with von Hippel-Lindau (VHL) disease. Identification of genotype-phenotype correlation is an important prerequisite for better management, treatment and prognosis.
Methods: Retrospective, single-centre cohort study of 200 VHL patients.
U1 small nuclear ribonucleoparticle (U1 snRNP) plays a central role during RNA processing. Previous structures of U1 snRNP revealed how the ribonucleoparticle is organized and recognizes the pre-mRNA substrate at the exon-intron junction. As with many other ribonucleoparticles involved in RNA metabolism, U1 snRNP contains extensions made of low complexity sequences.
View Article and Find Full Text PDFObjective: The choice of surgical technique in sight-threatening Grave orbitopathy remains controversial. Available data are mostly derived from mixed cohorts with multiple surgical indications and techniques. The authors assessed predictors for visual outcome after standardized pterional orbital decompression for dysthyroid optic neuropathy.
View Article and Find Full Text PDFPurpose: To quantify retinal vasculature changes in Stargardt disease1 (STGD1) with volume-rendered optical coherence tomography angiography.
Methods: Optical coherence tomography angiography volumes from healthy subjects and two subgroups of patients with STGD1 with the presence/absence of definitely decreased autofluorescence areas were compared. Optical coherence tomography angiography vessel surface area and vessel volume were measured in central zones (Z) of 1-, 2-, and 3-mm diameter.
Cellular life requires a high degree of molecular complexity and self-organization, some of which must have originated in a prebiotic context. Here, we demonstrate how both of these features can emerge in a plausibly prebiotic system. We found that chemical gradients in simple mixtures of activated amino acids and fatty acids can lead to the formation of amyloid-like peptide fibrils that are localized inside of a proto-cellular compartment.
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