Search results for "genetics [Antigens]"
showing 10 items of 2994 documents
The HMGB1 protein induces a metabolic type of tumour cell death by blocking aerobic respiration
2016
The high-mobility group box 1 (HMGB1) protein has a central role in immunological antitumour defense. Here we show that natural killer cell-derived HMGB1 directly eliminates cancer cells by triggering metabolic cell death. HMGB1 allosterically inhibits the tetrameric pyruvate kinase isoform M2, thus blocking glucose-driven aerobic respiration. This results in a rapid metabolic shift forcing cells to rely solely on glycolysis for the maintenance of energy production. Cancer cells can acquire resistance to HMGB1 by increasing glycolysis using the dimeric form of PKM2, and employing glutaminolysis. Consistently, we observe an increase in the expression of a key enzyme of glutaminolysis, malic …
Direct Visualization of the Conformational Dynamics of Single Influenza Hemagglutinin Trimers
2018
Influenza hemagglutinin (HA) is the canonical type I viral envelope glycoprotein and provides a template for the membrane-fusion mechanisms of numerous viruses. The current model of HA-mediated membrane fusion describes a static "spring-loaded" fusion domain (HA2) at neutral pH. Acidic pH triggers a singular irreversible conformational rearrangement in HA2 that fuses viral and cellular membranes. Here, using single-molecule Förster resonance energy transfer (smFRET)-imaging, we directly visualized pH-triggered conformational changes of HA trimers on the viral surface. Our analyses reveal reversible exchange between the pre-fusion and two intermediate conformations of HA2. Acidification of p…
Beyond the Transport Function of Import Receptors: What’s All the FUS about?
2018
Nuclear import receptors are central players in transporting protein cargoes into the nucleus. Moving beyond this role, four newly published articles describe a function in regulating supramolecular assemblies by fine-tuning the phase separating properties of RNA-binding proteins, which has implications for a variety of devastating neurodegenerative disorders.
Label-free quantification in ion mobility-enhanced data-independent acquisition proteomics.
2016
Unbiased data-independent acquisition (DIA) strategies have gained increased popularity in the field of quantitative proteomics. The integration of ion mobility separation (IMS) into DIA workflows provides an additional dimension of separation to liquid chromatography-mass spectrometry (LC-MS), and it increases the achievable analytical depth of DIA approaches. Here we provide a detailed protocol for a label-free quantitative proteomics workflow based on ion mobility-enhanced DIA, which synchronizes precursor ion drift times with collision energies to improve precursor fragmentation efficiency. The protocol comprises a detailed description of all major steps including instrument setup, filt…
Endogenous β-neurexins on axons and within synapses show regulated dynamic behavior
2021
Summary: Neurexins are key organizer molecules that regulate synaptic function and are implicated in autism and schizophrenia. β-neurexins interact with numerous cell adhesion and receptor molecules, but their neuronal localization remains elusive. Using single-molecule tracking and high-resolution microscopy to detect neurexin1β and neurexin3β in primary hippocampal neurons from knockin mice, we demonstrate that endogenous β-neurexins are present in fewer than half of excitatory and inhibitory synapses. Moreover, we observe a large extrasynaptic pool of β-neurexins on axons and show that axonal β-neurexins diffuse with higher surface mobility than those transiently confined within synapses…
Eukaryotic RNA Polymerases: The Many Ways to Transcribe a Gene
2021
In eukaryotic cells, three nuclear RNA polymerases (RNA pols) carry out the transcription from DNA to RNA, and they all seem to have evolved from a single enzyme present in the common ancestor with archaea. The multiplicity of eukaryotic RNA pols allows each one to remain specialized in the synthesis of a subset of transcripts, which are different in the function, length, cell abundance, diversity, and promoter organization of the corresponding genes. We hypothesize that this specialization of RNA pols has conditioned the evolution of the regulatory mechanisms used to transcribe each gene subset to cope with environmental changes. We herein present the example of the homeostatic regulation …
Different Within-Host Viral Evolution Dynamics in Severely Immunosuppressed Cases with Persistent SARS-CoV-2
2021
12 páginas, 2 figuras, 1 tabla.
Sentinel hospital-based surveillance for norovirus infection in children with gastroenteritis between 2015 and 2016 in Italy
2018
Noroviruses are one of the leading causes of gastro-enteric diseases worldwide in all age groups. Novel epidemic noroviruses with GII.P16 polymerase and GII.2 or GII.4 capsid type have emerged worldwide in late 2015 and in 2016. We performed a molecular epidemiological study of the noroviruses circulating in Italy to investigate the emergence of new norovirus strains. Sentinel hospital-based surveillance, in three different Italian regions, revealed increased prevalence of norovirus infection in children (<15 years) in 2016 (14.4% versus 9.8% in 2015) and the emergence of GII.P16 strains in late 2016, which accounted for 23.0% of norovirus infections. The majority of the strains with a GII.…
Nonlinear trade-offs allow the cooperation game to evolve from Prisoner's Dilemma to Snowdrift.
2017
[EN] The existence of cooperation, or the production of public goods, is an evolutionary problem. Cooperation is not favoured because the Prisoner s Dilemma (PD) game drives cooperators to extinction. We have re-analysed this problem by using RNA viruses to motivate a model for the evolution of cooperation. Gene products are the public goods and group size is the number of virions co-infecting the same host cell. Our results show that if the trade-off between replication and production of gene products is linear, PD is observed. However, if the trade-off is nonlinear, the viruses evolve into separate lineages of ultra-defectors and ultra-cooperators as group size is increased. The nonlinear…
The impact of the 2015/2016 El Niño on global photosynthesis using satellite remote sensing
2018
The El Niño-Southern Oscillation exerts a large influence on global climate regimes and on the global carbon cycle. Although El Niño is known to be associated with a reduction of the global total land carbon sink, results based on prognostic models or measurements disagree over the relative contribution of photosynthesis to the reduced sink. Here, we provide an independent remote sensing-based analysis on the impact of the 2015–2016 El Niño on global photosynthesis using six global satellite-based photosynthesis products and a global solar-induced fluorescence (SIF) dataset. An ensemble of satellite-based photosynthesis products showed a negative anomaly of −0.7 ± 1.2 PgC in 2015, but a sli…