Biology subjects

Möller, L.

Publications and source records attributed to Möller, L..

3 recordsLinked to original sources

bioRxiv2023

First virological and pathological study of Göttingen Minipigs with Dippity Pig Syndrome (DPS)

Dippity Pig Syndrome (DPS) is a well-known but rare complex of clinical signs affecting minipigs, which has not been thoroughly investigated yet. Clinically affected animals show acute appearance of red, exudating lesions across the spine. The lesions are painful, evidenced by arching of the back (dipping), and the onset of clinical symptoms is generally sudden. In order to understand the pathogenesis, histological and virological investigations were performed in affected and unaffected Gottingen Minipigs (GoMPs). The following DNA viruses were screened for using PCR-based methods: Porcine cytomegalovirus (PCMV), which is a porcine roseolovirus (PCMV/PRV), porcine lymphotropic herpesviruses (PLHV-1, PLHV-2, PLHV-3), porcine circoviruses (PCV1, PCV2, PCV3, PCV4), porcine parvovirus 1 (PPV1), and Torque Teno sus virus (TTSuV1, TTSuV2). Screening was also performed for integrated porcine endogenous retroviruses (PERV-A, PERV-B, PERV-C) and recombinant PERV-A/C and their expression as well as for the RNA viruses hepatitis E virus (HEV) and SARS-CoV-2. Eight clinically affected and one unaffected GoMPs were analyzed. Additional unaffected minipigs had been analyzed in the past. The analyzed GoMPs contained PERV-A and PERV-B integrated in the genome, which are present in all pigs and PERV-C, which is present in most, but not all pigs. In one affected GoMPs recombinant PERV-A/C was detected in blood. In this animal a very high expression of PERV mRNA was observed. PCMV/PRV was found in three affected animals, PCV1 was found in three animals with DPS and in the healthy minipig, and PCV3 was detected in two animals with DPS and in the unaffected minipig. Most importantly, in one animal only PLHV-3 was detected. It was found in the affected and unaffected skin, and in other organs. Unfortunately, PLHV-3 could not be studied in all other affected minipigs. None of the other viruses were detected and using electron microscopy, no virus particles were found in the affected skin. This data identified some virus infections in GoMPs with DPS and assign a special role to PLHV-3. Since PCMV/PRV, PCV1, PCV3 and PLHV-3 were also found in unaffected animals, a multifactorial cause of DPS is suggested. However, elimination of the viruses from GoMPs may prevent DPS.

microbiology↗

bioRxiv2019

Amphipathic helices of cellular proteins can replace the helix in M2 of Influenza A virus with only small effects on virus replication

M2 of influenza virus functions as proton channel during virus entry. In addition, an amphipathic helix in its cytoplasmic tail plays a role during budding. It targets M2 to the assembly site where it inserts into the inner membrane leaflet to induce curvature that causes virus scission. Since vesicularisation of membranes can be performed by a variety of amphiphilic peptides we used reverse genetics to investigate whether they can substitute for M2s helix.\n\nVirus could not be generated if M2s helix was deleted or replaced by a peptide predicted not to form an amphiphilic helix. In contrast, viruses could be rescued if the M2 helix was exchanged by helices known to induce membrane curvature. Infectious virus titers were marginally reduced if M2 contains the helix of the amphipathic lipid packing sensor, from the Epsin N-Terminal Homology domain or the non-natural membrane inducer RW16. Transmission EM of infected cells did not reveal unequivocal evidence that virus budding or membrane scission was disturbed in any of the mutants. Instead, individual virus mutants exhibit other defects in M2, such as reduced surface expression, incorporation into virus particles and ion channel activity. The protein composition and specific infectivity was also altered for mutant virions. We conclude that the presence of an amphiphilic helix in M2 is essential for virus replication, but other helices can replace its basic (curvature-inducing) function.\n\nImportanceInfluenza is unique among enveloped viruses since it does not rely on the cellular ESCRT-machinery for budding. Instead viruses encode their own scission machine, the M2 protein. M2 is targeted to the edge of the viral assembly site where it inserts an amphiphilic helix into the membrane to induce curvature. Cellular proteins utilize a similar mechanism for scission of vesicles. We show that the helix of M2 can be replaced by helices from cellular proteins with only small effects on virus replication. No evidence was obtained that budding is disturbed, but individual mutants exhibit other defects in M2 which explain the reduced virus titers. In contrast, no virus could be generated if the helix of M2 is deleted or replaced by irrelevant sequences. These experiments support the concept that M2 requires an amphiphilic helix to induce membrane curvature, but its biophysical properties are more important than the amino acid sequence.

cell biology↗

bioRxiv2018

The Time Course of Ineffective Sham Blinding During 1mA tDCS

BackgroundStudies using transcranial direct current stimulation (tDCS) typically compare the effects of an active (10-30min) relative to a shorter sham (placebo) protocol. Both active and sham tDCS are presumed to be perceptually identical on the scalp, and thus represent an effective method of delivering double-blinded experimental designs. However, participants often show above-chance accuracy when asked which condition involved active/sham retrospectively.\n\nObjective/HypothesisWe aimed to assess the time course of sham-blinding during active and sham tDCS. We predicted that 1) Participants will be aware that the current is switched on for a longer duration in the active versus the sham protocol, 2) Active anodal tDCS will reduce reaction times more effectively than sham.\n\nMethods32 adults were tested in a pre-registered, double-blinded, within-subjects design. A forced-choice reaction time task was undertaken before, during and after active (10min 1mA) and sham (20s 1mA) tDCS. The anode was placed over the left primary motor cortex (C3) to target the right hand, and the cathode on the right forehead. Two probe questions were asked every 30s: \"Is the stimulation on? \"and \"How sure are you?\".\n\nResultsDistinct periods of non-overlapping confidence intervals were identified between the active and sham conditions, totalling 5min (57.1% of the total difference in stimulation time). These began immediately after sham ramp-down and lasted until the active protocol had ended. Active tDCS had no effect on reaction times compared to sham ({Delta}RT active vs sham p>0.38 in all blocks).\n\nConclusionsWe show a failure of placebo control during low-intensity tDCS.

neuroscience↗