Drosophila STING protein has a role in lipid metabolism
Stimulator of interferon genes (STING) plays an important role in innate immunity by controlling type I interferon response against invaded pathogens. In this work we describe a previously unknown role of STING in lipid metabolism inDrosophila. Flies withSTING deletion are sensitive to starvation and oxidative stress, have reduced lipid storage and downregulated expression of lipid metabolism genes. We found thatDrosophila STING interacts with lipid synthesizing enzymes acetyl-CoA carboxylase (ACC) and fatty acid synthase (FASN). ACC and FASN also interact with each other, indicating that all three proteins may be componen...
Source: eLife - September 1, 2021 Category: Biomedical Science Tags: Biochemistry and Chemical Biology Genetics and Genomics Source Type: research
Correction of amblyopia in cats and mice after the critical period
Monocular deprivation early in development causes amblyopia, a severe visual impairment. Prognosis is poor if therapy is initiated after an early critical period. However, clinical observations have shown that recovery from amblyopia can occur later in life when the non-deprived (fellow) eye is removed. The traditional interpretation of this finding is that vision is improved simply by the elimination of interocular suppression in primary visual cortex, revealing responses to previously subthreshold input. However, an alternative explanation is that silencing activity in the fellow eye establishes conditions in visual cort...
Source: eLife - August 31, 2021 Category: Biomedical Science Tags: Neuroscience Source Type: research
YAP and TAZ are transcriptional co-activators of AP-1 proteins and STAT3 during breast cellular transformation
The YAP and TAZ paralogs are transcriptional co-activators recruited to target sites by TEAD proteins. Here, we show that YAP and TAZ are also recruited by JUNB (a member of the AP-1 family) and STAT3, key transcription factors that mediate an epigenetic switch linking inflammation to cellular transformation. YAP and TAZ directly interact with JUNB and STAT3 via a WW domain important for transformation, and they stimulate transcriptional activation by AP-1 proteins. JUNB, STAT3, and TEAD co-localize at virtually all YAP/TAZ target sites, yet many target sites only contain individual AP-1, TEAD, or STAT3 motifs. This observ...
Source: eLife - August 31, 2021 Category: Biomedical Science Tags: Cancer Biology Chromosomes and Gene Expression Source Type: research
TGF β signalling is required to maintain pluripotency of human naïve pluripotent stem cells
The signalling pathways that maintain primed human pluripotent stem cells (hPSCs) have been well characterised, revealing a critical role for TGF β/Activin/Nodal signalling. In contrast, the signalling requirements of naive human pluripotency have not been fully established. Here, we demonstrate that TGFβ signalling is required to maintain naive hPSCs. The downstream effector proteins – SMAD2/3 – bind common sites in naive and primed hP SCs, including shared pluripotency genes. In naive hPSCs, SMAD2/3 additionally bind to active regulatory regions near to naive pluripotency genes. Inhibiting TGFβ signalling in naive...
Source: eLife - August 31, 2021 Category: Biomedical Science Tags: Stem Cells and Regenerative Medicine Source Type: research
What can we learn from honey bees?
The Western honey bee provides a model system for studying how closely related species of bacteria are able to coexist in a single community. (Source: eLife)
Source: eLife - August 31, 2021 Category: Biomedical Science Tags: Ecology Microbiology and Infectious Disease Source Type: research
Leveraging the mendelian disorders of the epigenetic machinery to systematically map functional epigenetic variation
Although each Mendelian Disorder of the Epigenetic Machinery (MDEM) has a different causative gene, there are shared disease manifestations. We hypothesize that this phenotypic convergence is a consequence of shared epigenetic alterations. To identify such shared alterations we interrogate chromatin (ATAC-Seq) and expression (RNA-Seq) states in B cells from three MDEM mouse models (Kabuki (KS) types 1&2 and Rubinstein-Taybi (RT1) syndromes). We develop a new approach for the overlap analysis and find extensive overlap primarily localized in gene promoters. We show that disruption of chromatin accessibility at promoters oft...
Source: eLife - August 31, 2021 Category: Biomedical Science Tags: Computational and Systems Biology Genetics and Genomics Source Type: research
Spectral signature and behavioral consequence of spontaneous shifts of pupil-linked arousal in human
Arousal levels perpetually rise and fall spontaneously. How markers of arousal - pupil size and frequency content of brain activity - relate to each other and influence behavior in humans is poorly understood. We simultaneously monitored magnetoencephalography and pupil in healthy volunteers at rest and during a visual perceptual decision-making task. Spontaneously varying pupil size correlates with power of brain activity in most frequency bands across large-scale resting-state cortical networks. Pupil size recorded at prestimulus baseline correlates with subsequent shifts in detection bias (c) and sensitivity (d'). When ...
Source: eLife - August 31, 2021 Category: Biomedical Science Tags: Neuroscience Source Type: research
Edge-strand of BepA interacts with immature LptD on the β-barrel assembly machine to direct it to on- and off-pathways
The outer membrane (OM) of gram-negative bacteria functions as a selective permeability barrier.Escherichia coli periplasmic Zn-metallopeptidase BepA contributes to the maintenance of OM integrity through its involvement in the biogenesis and degradation of LptD, a β-barrel protein component of the lipopolysaccharide translocon. BepA either promotes the maturation of LptD when it is on the normal assembly pathway (on-pathway) or degrades it when its assembly is compromised (off-pathway). BepA performs these functions probably on the β‐barrel assembly machi nery (BAM) complex. However, how BepA recognizes and directs an...
Source: eLife - August 31, 2021 Category: Biomedical Science Tags: Biochemistry and Chemical Biology Cell Biology Source Type: research
Mutational sources of < i > trans < /i > -regulatory variation affecting gene expression in < i > Saccharomyces cerevisiae < /i >
Heritable variation in a gene ’s expression arises from mutations impactingcis- andtrans-acting components of its regulatory network. Here, we investigate howtrans-regulatory mutations are distributed within the genome and within a gene regulatory network by identifying and characterizing 69 mutations withtrans-regulatory effects on expression of the same focal gene inSaccharomyces cerevisiae. Relative to 1766 mutations without effects on expression of this focal gene, we found that thesetrans-regulatory mutations were enriched in coding sequences of transcription factors previously predicted to regulate expression of th...
Source: eLife - August 31, 2021 Category: Biomedical Science Tags: Evolutionary Biology Genetics and Genomics Source Type: research
Thrombopoietin from hepatocytes promotes hematopoietic stem cell regeneration after myeloablation
The bone marrow niche plays a critical role in hematopoietic recovery and hematopoietic stem cell (HSC) regeneration after myeloablative stress. However, it is not clear whether systemic factors beyond the local niche are required for these essential processesin vivo. Thrombopoietin (THPO) is a critical cytokine promoting hematopoietic rebound after myeloablation and its transcripts are expressed by multiple cellular sources. The upregulation of bone marrow-derived THPO has been proposed to be crucial for hematopoietic recovery and HSC regeneration after stress. Nonetheless, the cellular source of THPO in myeloablative str...
Source: eLife - August 31, 2021 Category: Biomedical Science Tags: Stem Cells and Regenerative Medicine Source Type: research
Studying evolution of the primary body axis in vivo and in vitro
The metazoan body plan is established during early embryogenesis via collective cell rearrangements and evolutionarily conserved gene networks, as part of a process commonly referred to as gastrulation. While substantial progress has been achieved in terms of characterizing the embryonic development of several model organisms, underlying principles of many early patterning processes nevertheless remain enigmatic. Despite the diversity of (pre-)gastrulating embryo and adult body shapes across the animal kingdom, the body axes, which are arguably the most fundamental features, generally remain identical between phyla. Recent...
Source: eLife - August 31, 2021 Category: Biomedical Science Tags: Developmental Biology Evolutionary Biology Source Type: research
The mechanism of MICU-dependent gating of the mitochondrial Ca < sup > 2+ < /sup > uniporter
Ca2+ entry into mitochondria is through the mitochondrial calcium uniporter complex (MCUcx), a Ca2+-selective channel composed of five subunit types. Two MCUcx subunits (MCU and EMRE) span the inner mitochondrial membrane, while three Ca2+-regulatory subunits (MICU1, MICU2 and MICU3) reside in the intermembrane space. Here we provide rigorous analysis of Ca2+ and Na+ fluxes via MCUcx in intact isolated mitochondria to understand the function of MICU subunits. We also perform direct patch clamp recordings of macroscopic and single MCUcx currents to gain further mechanistic insight. This comprehensive analysis shows that the...
Source: eLife - August 31, 2021 Category: Biomedical Science Tags: Structural Biology and Molecular Biophysics Source Type: research
Sterically confined rearrangements of SARS-CoV-2 Spike protein control cell invasion
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is highly contagious, and transmission involves a series of processes that may be targeted by vaccines and therapeutics. During transmission, host cell invasion is controlled by a large-scale (200 –300 Å) conformational change of the Spike protein. This conformational rearrangement leads to membrane fusion, which creates transmembrane pores through which the viral genome is passed to the host. During Spike-protein-mediated fusion, the fusion peptides must be released from the core of the p rotein and associate with the host membrane. While infection relies on ...
Source: eLife - August 31, 2021 Category: Biomedical Science Tags: Structural Biology and Molecular Biophysics Source Type: research
Inducible and reversible inhibition of miRNA-mediated gene repression < i > in vivo < /i >
Although virtually all gene networks are predicted to be controlled by miRNAs, the contribution of this important layer of gene regulation to tissue homeostasis in adult animals remains unclear. Gain and loss of function experiments have provided key insights into the specific function of individual miRNAs, but effective genetic tools to study the functional consequences of global inhibition of miRNA activityin vivo are lacking. Here we report the generation and characterization of a genetically engineered mouse strain in which miRNA-mediated gene repression can be reversibly inhibited without affecting miRNA biogenesis or...
Source: eLife - August 31, 2021 Category: Biomedical Science Tags: Cell Biology Stem Cells and Regenerative Medicine Source Type: research
Decoding the brain state-dependent relationship between pupil dynamics and resting state fMRI signal fluctuation
Pupil dynamics serve as a physiological indicator of cognitive processes and arousal states of the brain across a diverse range of behavioral experiments. Pupil diameter changes reflect brain state fluctuations driven by neuromodulatory systems. Resting state fMRI (rs-fMRI) has been used to identify global patterns of neuronal correlation with pupil diameter changes, however, the linkage between distinct brain state-dependent activation patterns of neuromodulatory nuclei with pupil dynamics remains to be explored. Here, we identified four clusters of trials with unique activity patterns related to pupil diameter changes in...
Source: eLife - August 31, 2021 Category: Biomedical Science Tags: Neuroscience Source Type: research
