Variation in human herpesvirus 6B telomeric integration, excision and transmission between tissues and individuals
Human herpesviruses 6A and 6B (HHV-6A/6B) are ubiquitous pathogens that persist lifelong in latent form and can cause severe conditions upon reactivation. They are spread by community-acquired infection of free virus (acqHHV6A/6B) and by germline transmission of inherited chromosomally-integrated HHV-6A/6B (iciHHV-6A/6B) in telomeres. We exploited a hypervariable region of the HHV-6B genome to investigate the relationship between acquired and inherited virus and revealed predominantly maternal transmission of acqHHV-6B in families. Remarkably, we demonstrate that some copies of acqHHV-6B in saliva from healthy adults gaine...
Source: eLife - September 21, 2021 Category: Biomedical Science Tags: Genetics and Genomics Microbiology and Infectious Disease Source Type: research
Vaccination induces rapid protection against bacterial pneumonia via training alveolar macrophage in mice
Vaccination strategies for rapid protection against multidrug-resistant bacterial infection are very important, especially for hospitalized patients who have high risk of exposure to these bacteria. However, few such vaccination strategies exist due to a shortage of knowledge supporting their rapid effect. Here, we demonstrated that a single intranasal immunization of inactivated whole cell ofAcinetobacter baumannii elicits rapid protection against broadA. baumannii-infected pneumonia via training of innate immune response inRag1-/- mice. Immunization-trained alveolar macrophages (AMs) showed enhanced TNF- α production up...
Source: eLife - September 20, 2021 Category: Biomedical Science Tags: Immunology and Inflammation Microbiology and Infectious Disease Source Type: research
SMA-miRs: miR-181a-5p, -324-5p, -451a are overexpressed in spinal muscular atrophy skeletal muscle and serum samples
(Source: eLife)
Source: eLife - September 20, 2021 Category: Biomedical Science Tags: Genetics and Genomics Medicine Source Type: research
Social-like responses are inducible in asocial Mexican cavefish despite the exhibition of strong repetitive behaviour
Social behaviour is a hallmark of complex animal systems; however, some species appear to have secondarily lost this social ability. In these non-social species, whether social abilities are permanently lost or suppressed is unclear. The blind cavefishAstyanax mexicanus is known to be asocial. Here, we reveal that cavefish exhibited social-like interactions in familiar environments but suppressed these interactions in stress-associated unfamiliar environments. Furthermore, the level of suppression in sociality was positively correlated with that of stereotypic repetitive behaviour, as seen in mammals. Treatment with a huma...
Source: eLife - September 20, 2021 Category: Biomedical Science Tags: Ecology Evolutionary Biology Source Type: research
Circular RNA repertoires are associated with evolutionarily young transposable elements
Circular RNAs (circRNAs) are found across eukaryotes and can function in post-transcriptional gene regulation. Their biogenesis through a circle-forming backsplicing reaction is facilitated by reverse-complementary repetitive sequences promoting pre-mRNA folding. Orthologous genes from which circRNAs arise, overall contain more strongly conserved splice sites and exons than other genes, yet it remains unclear to what extent this conservation reflects purifying selection acting on the circRNAs themselves. Our analyses of circRNA repertoires from five species representing three mammalian lineages (marsupials, eutherians: rod...
Source: eLife - September 20, 2021 Category: Biomedical Science Tags: Evolutionary Biology Genetics and Genomics Source Type: research
Diverse inhibitory projections from the cerebellar interposed nucleus
The cerebellum consists of parallel circuit modules that contribute to diverse behaviors, spanning motor to cognitive. Recent work employing cell-type specific tracing has identified circumscribed output channels of the cerebellar nuclei that could confer tight functional specificity. These studies have largely focused on excitatory projections of the cerebellar nuclei, however, leaving open the question of whether inhibitory neurons also constitute multiple output modules. We mapped output and input patterns to intersectionally restricted cell types of the interposed and adjacent interstitial nuclei in mice. In contrast t...
Source: eLife - September 20, 2021 Category: Biomedical Science Tags: Neuroscience Source Type: research
Temporo-cerebellar connectivity underlies timing constraints in audition
The flexible and efficient adaptation to dynamic, rapid changes in the auditory environment likely involves generating and updating of internal models. Such models arguably exploit connections between the neocortex and the cerebellum, supporting proactive adaptation. Here we tested whether temporo-cerebellar disconnection is associated with the processing of sound at short-timescales. First, we identify lesion-specific deficits for the encoding of short timescale spectro-temporal non-speech and speech properties in patients with left posterior temporal cortex stroke. Second, using lesion- guided probabilistic tractography ...
Source: eLife - September 20, 2021 Category: Biomedical Science Tags: Neuroscience Source Type: research
Developmental change in prefrontal cortex recruitment supports the emergence of value-guided memory
Prioritizing memory for valuable information can promote adaptive behavior across the lifespan, but it is unclear how the neurocognitive mechanisms that enable the selective acquisition of useful knowledge develop. Here, using a novel task coupled with functional magnetic resonance imaging, we examined how children, adolescents, and adults (N = 90) learn from experience what information is likely to be rewarding, and modulate encoding and retrieval processes accordingly. We found that the ability to use learned value signals to selectively enhance memory for useful information strengthened throughout childhood and into ado...
Source: eLife - September 20, 2021 Category: Biomedical Science Tags: Neuroscience Source Type: research
Condensation tendency and planar isotropic actin gradient induce radial alignment in confined monolayers
A monolayer of highly motile cells can establish long-range orientational order, which can be explained by hydrodynamic theory of active gels and fluids. However, it is less clear how cell shape changes and rearrangement are governed when the monolayer is in mechanical equilibrium states when cell motility diminishes. In this work, we report that rat embryonic fibroblasts (REF), when confined in circular mesoscale patterns on rigid substrates, can transition from the spindle shapes to more compact morphologies. Cells align radially only at the pattern boundary when they are in the mechanical equilibrium. This radial alignm...
Source: eLife - September 20, 2021 Category: Biomedical Science Tags: Physics of Living Systems Source Type: research
Evolutionary dynamics of circular RNAs in primates
Many primate genes produce circular RNAs (circRNAs). However, the extent of circRNA conservation between closely related species remains unclear. By comparing tissue-specific transcriptomes across over 70 million years of primate evolution, we identify that within 3 million years circRNA expression profiles diverged such that they are more related to species identity than organ type. However, our analysis also revealed a subset of circRNAs with conserved neural expression across tens of millions of years of evolution. By comparing to species-specific circRNAs, we identified that the downstream intron of the conserved circR...
Source: eLife - September 20, 2021 Category: Biomedical Science Tags: Evolutionary Biology Genetics and Genomics Source Type: research
Synaptotagmin 7 is targeted to the axonal plasma membrane through γ-secretase processing to promote synaptic vesicle docking in mouse hippocampal neurons
Synaptotagmin 7 (SYT7) has emerged as a key regulator of presynaptic function, but its localization and precise role in the synaptic vesicle cycle remain the subject of debate. Here, we used iGluSnFR to optically interrogate glutamate release, at the single-bouton level, in SYT7KO-dissociated mouse hippocampal neurons. We analyzed asynchronous release, paired-pulse facilitation, and synaptic vesicle replenishment and found that SYT7 contributes to each of these processes to different degrees. ‘Zap-and-freeze’ electron microscopy revealed that a loss of SYT7 diminishes docking of synaptic vesicles after a stimulus and i...
Source: eLife - September 20, 2021 Category: Biomedical Science Tags: Neuroscience Source Type: research
Maturation of Purkinje cell firing properties relies on neurogenesis of excitatory neurons
Preterm infants that suffer cerebellar insults often develop motor disorders and cognitive difficulty. Excitatory granule cells, the most numerous neuron type in the brain, are especially vulnerable and likely instigate disease by impairing the function of their targets, the Purkinje cells. Here, we use regional genetic manipulations and in vivo electrophysiology to test whether excitatory neurons establish the firing properties of Purkinje cells during postnatal mouse development. We generated mutant mice that lack the majority of excitatory cerebellar neurons and tracked the structural and functional consequences on Purk...
Source: eLife - September 20, 2021 Category: Biomedical Science Tags: Developmental Biology Neuroscience Source Type: research
A two-stage solution
The parasite that causes African sleeping sickness can be transmitted from mammals to tsetse flies in two stages of its lifecycle, rather than one as was previously thought. (Source: eLife)
Source: eLife - September 17, 2021 Category: Biomedical Science Tags: Microbiology and Infectious Disease Source Type: research
Structural characterization of NrnC identifies unifying features of dinucleotidases
RNA degradation is fundamental for cellular homeostasis. The process is carried out by various classes of endolytic and exolytic enzymes that together degrade an RNA polymer to mono-ribonucleotides. Within the exoribonucleases, nano-RNases play a unique role as they act on the smallest breakdown products and hence catalyze the final steps in the process. We recently showed that oligoribonuclease (Orn) acts as a dedicated diribonucleotidase, defining the ultimate step in RNA degradation that is crucial for cellular fitness (Kim et al., 2019). Whether such a specific activity exists in organisms that lack Orn-type exoribonuc...
Source: eLife - September 17, 2021 Category: Biomedical Science Tags: Microbiology and Infectious Disease Structural Biology and Molecular Biophysics Source Type: research
Gamete expression of TALE class HD genes activates the diploid sporophyte program in < i > Marchantia polymorpha < /i >
Eukaryotic life cycles alternate between haploid and diploid phases and in phylogenetically diverse unicellular eukaryotes, expression of paralogous homeodomain genes in gametes primes the haploid-to-diploid transition. In the unicellular Chlorophyte algaChlamydomonas KNOX and BELL TALE-homeodomain genes mediate this transition. We demonstrate that in the liverwortMarchantia polymorpha paternal (sperm) expression of three of five phylogenetically diverse BELL genes, MpBELL234, and maternal (egg) expression of both MpKNOX1 and MpBELL34mediate the haploid-to-diploid transition. Loss-of-function alleles of MpKNOX1 result in z...
Source: eLife - September 17, 2021 Category: Biomedical Science Tags: Developmental Biology Evolutionary Biology Source Type: research
