The CR3 motif of Rrp44p is important for interaction with the core exosome and exosome function

The 10-subunit RNA exosome is involved in a large number of diverse RNA processing and degradation events in eukaryotes. These reactions are carried out by the single catalytic subunit, Rrp44p/Dis3p, which is composed of three parts that are conserved throughout eukaryotes. The exosome is named for the 3′ to 5′ exoribonuclease activity provided by a large C-terminal region of the Rrp44p subunit that resembles other exoribonucleases. Rrp44p also contains an endoribonuclease domain. Finally, the very N-terminus of Rrp44p contains three Cys residues (CR3 motif) that are conserved in many eukaryotes but have no known function. These three conserved Cys residues cluster with a previously unrecognized conserved His residue in what resembles a metal-ion-binding site. Genetic and biochemical data show that this CR3 motif affects both endo- and exonuclease activity in vivo and both the nuclear and cytoplasmic exosome, as well as the ability of Rrp44p to associate with the other exosome subunits. These data provide the first direct evidence that the exosome-Rrp44p interaction is functionally important and also provides a molecular explanation for the functional defects when the conserved Cys residues are mutated.     

Simultaneous binding of Guidance Cues NET1 and RGM blocks extracellular NEO1 signaling

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A taxonomy of transcriptomic cell types across the isocortex and hippocampal formation

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Low-dose Ad26.COV2.S protection against SARS-CoV-2 challenge in rhesus macaques

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Profiling of Volatile Organic Compounds in Exhaled Breath As a Strategy to Find Early Predictive Signatures of Asthma in Children

Wheezing is one of the most common respiratory symptoms in preschool children under six years old. Currently, no tests are available that predict at early stage who will develop asthma and who will be a transient wheezer. Diagnostic tests of asthma are reliable in adults but the same tests are difficult to use in children, because they are invasive and require active cooperation of the patient. A non-invasive alternative is needed for children. Volatile Organic Compounds (VOCs) excreted in breath could yield such non-invasive and patient-friendly diagnostic. The aim of this study was to identify VOCs in the breath of preschool children (inclusion at age 2–4 years) that indicate preclinical asthma. For that purpose we analyzed the total array of exhaled VOCs with Gas Chromatography time of flight Mass Spectrometry of 252 children between 2 and 6 years of age. Breath samples were collected at multiple time points of each child. Each breath-o-gram contained between 300 and 500 VOCs; in total 3256 different compounds were identified across all samples. Using two multivariate methods, Random Forests and dissimilarity Partial Least Squares Discriminant Analysis, we were able to select a set of 17 VOCs which discriminated preschool asthmatic children from transient wheezing children. The correct prediction rate was equal to 80% in an independent test set. These VOCs are related to oxidative stress caused by inflammation in the lungs and consequently lipid peroxidation. In conclusion, we showed that VOCs in the exhaled breath predict the subsequent development of asthma which might guide early treatment.     

The Burden of Research on Trauma for Respondents: A Prospective and Comparative Study on Respondents Evaluations and Predictors

The possible burden of participating in trauma research is an important topic for Ethical Committees (EC''s), Review Boards (RB''s) and researchers. However, to what extent research on trauma is more burdensome than non-trauma research is unknown. Little is known about which factors explain respondents evaluations on the burden: to what extent are they trauma-related or dependent on other factors such as personality and how respondents evaluate research in general? Data of a large probability based multi-wave internet panel, with surveys on politics and values, personality and health in 2009 and 2011, and a survey on trauma in 2012 provided the unique opportunity to address these questions. Results among respondents confronted with these events in the past 2 years (N = 950) showed that questions on trauma were significantly and systematically evaluated as less pleasant (enjoyed less), more difficult, but also stimulated respondents to think about things more than almost all previous non-trauma surveys. Yet, the computed effect sizes indicated that the differences were (very) small and often meaningless. No differences were found between users and non-users of mental services, in contrast to posttraumatic stress symptoms. Evaluations of the burden of previous surveys in 2011 on politics and values, personality and health most strongly, systematically and independently predicted the burden of questions on trauma, and not posttraumatic stress symptoms, event-related coping self-efficacy and personality factors. For instance, multiple linear regression analyses showed that 30% of the variance of how (un)pleasant questions on trauma and life-events were evaluated, was explained by how (un)pleasant the 3 surveys in 2011 were evaluated, in contrast to posttraumatic stress symptoms (not significant) and coping self-efficacy (5%). Findings question why EC''s, RB''s and researchers should be more critical of the possible burden of trauma research than of the possible burden of other non-trauma research.     

Orientation in the dark: brain circuits involved in the perception of electric signals in mormyrid electric fish.

Weakly electric fish produce electric signals with a specialised organ in their tail. In addition, they are electrosensitive and can perceive their self-generated signals (for electrolocation) and electric signals of other electric fishes (for electrocommunication). Mormyrids possess three types of peripheral electroreceptor organs, one used for electrocommunication and two types involved in electolocation. They are innervated by afferent fibres, which project to different zones in the electrosensory lateral line lobe (ELL) in the medulla. Brain circuits for electrolocation and electrocommunication are separated almost throughout the whole brain. Electrolocation pathways run from the ELL-cortex to the torus semicircularis of the midbrain and then via the valvula cerebelli towards the telencephalon. Pathways involved in electrocommunication run from the nucleus of the ELL to another part of the torus and from there through the isthmic granule nucleus to the valvula. In addition, a pathway via the preglomerular complex to the telencephalon might exist. In both the electrolocation and the electrocommunication circuits, prominent recurrent pathways are present.     

Changes in interactions between juniper and mistletoe mediated by shared avian frugivores: parasitism to potential mutualism

Although mistletoe is typically viewed as a parasite of juniper in a two-way interaction, its role may become neutral or even mutualistic when their common avian seed dispersing agents are considered as a three-way interaction. In the study area, wintering avian frugivores forage on both one-seed juniper (Juniperus monosperma) berries and on the fruit of its associated mistletoe (Phoradendron juniperinum). Three major findings emerged from our studies that support a three-way interaction and the hypothesis of conditional interactions. First, mistletoes provide a stable resource for shared avian seed dispersers; junipers do not. Whereas juniper berry production varied 10- to 15-fold over the 3 years of our study, mistletoe fruit abundance did not vary significantly. Second, the abundance of avian seed dispersal agents, such as Townsend's solitaires (Myadestes townsendi), is strongly tied to the abundance of juniper berries in mast years and mistletoe fruits in all years. In fact, the best overall predictor of their common avian seed dispersal agents was the abundance of mistletoe; stands with mistletoe attracted up to 3 times more avian frugivores than stands with little or no mistletoe. Thus, mistletoe berries can serve as the main attractor for birds that disperse juniper berries. Third, in agreement with the hypothesis that mistletoe can benefit junipers by attracting and supporting greater populations of avian seed dispersal agents, the number of juniper seedlings was more than 2-fold greater in stands with high mistletoe density compared with stands that had little or no mistletoe. Results suggest that the occurrence of a three-way interaction, in the presence of environmental variation (in this case, annual variation in juniper berry crops), may change the ecological roles of associated species. A conceptual model is presented to illustrate how the role of mistletoe may range from parasitic to mutualistic, while the role of avian seed dispersers may conversely range from mutualistic to parasitic, the latter by acting as vectors for the spread of mistletoe.     

Preface to Mechanisms of neuromuscular control. A Theme organized and edited by J. L. van Leeuwen

Preface to Mechanisms of neuromuscular control. A Theme organized and edited by J. L. van Leeuwen.