pinecone/core-2020-05-10-deduplication huggingface dataset:
Evidence for a novel cytoplasmic processing event in ribosome maturation in the sea urchin Paracentrotus lividus.

In this paper we demonstrate the existence of a cytoplasmic processing step, never before described, involving both the pre-ribosomal subunits in the sea urchin Paracentrotus lividus. Northern-blot hybridization, primer extension, S1 mapping experiments and in situ hybridizations allowed us to demonstrate that cytoplasmic processed particles are successively re-imported into the nucleus where maturation of their RNAs is completed prior to being exported to the cytoplasm. Our findings lead to the proposal of a new model of ribosome maturation and shuttling
Ultrastructural and quantitative analysis of the lipid droplet clustering induced by hepatitis C virus core protein.
 : 
HCV-induced lipid droplet clustering

International audienceHepatitis C virus (HCV) release is linked to the formation of lipid droplet (LD) clusters in the perinuclear area of infected cells, induced by the core protein. We used electron microscopy (EM) to monitor and compare the number and size of LD in cells producing the mature and immature forms of the HCV core protein, and 3D EM to reconstruct whole cells producing the mature core protein. Only the mature protein coated the LD and induced their clustering and emergence from endoplasmic reticulum membranes enriched in this protein. We found no particular association between LD clusters and the centrosome in reconstructed cells. The LD clustering induced by the mature core protein was associated with an increase in LD synthesis potentially due, at least in part, to the ability of this protein to coat the LD. These observations provide useful information for further studies of the mechanisms involved in HCV-induced steatosis
Structure and function of interleukin-22 and other members of the interleukin-10 family

The IL-10 family of cytokines is comprised of IL-10, IL-19, IL-20, IL-22, IL-24, IL-26, and IFN-λs (IL-28A, IL-28B, and IL-29). The IL-10 family members bind to shared class II cytokine receptor chains that associate in various combinations in heterodimeric complexes. Upon interleukin/receptor complex formation, these proteins switch on the Jak/STAT pathway and elicit pleiotropic biological responses whose variety sharply contrasts with their structural similarities. IL-10 family members are involved in several human diseases and health conditions and hence their structural analyses may provide valuable information to design specific therapeutic strategies. In this review, we describe the human interleukin-10 family of cytokines, focusing on their structures and functions, with particular attention given to IL-22 and IL-10. We report on the recently published structures of IL-10 cytokine family members and their complexes with cognate transmembrane and soluble receptors as well as on interleukin physiology and physiopathology
Enhanced susceptibility of T lymphocytes to oxidative stress in the absence of the cellular prion protein.
 : 
PrPC and oxidative stress in T lymphocytes

International audienceThe cellular prion glycoprotein (PrP(C)) is ubiquitously expressed but its physiologic functions remain enigmatic, particularly in the immune system. Here, we demonstrate in vitro and in vivo that PrP(C) is involved in T lymphocytes response to oxidative stress. By monitoring the intracellular level of reduced glutathione, we show that PrP(-/-) thymocytes display a higher susceptibility to H(2)O(2) exposure than PrP(+/+) cells. Furthermore, we find that in mice fed with a restricted diet, a regimen known to increase the intracellular level of ROS, PrP(-/-) thymocytes are more sensitive to oxidative stress. PrP(C) function appears to be specific for oxidative stress, since no significant differences are observed between PrP(-/-) and PrP(+/+) mice exposed to other kinds of stress. We also show a marked evolution of the redox status of T cells throughout differentiation in the thymus. Taken together, our results clearly ascribe to PrP(C) a protective function in thymocytes against oxidative stress
Poly(ADP-ribose)glycohydrolase is an upstream regulator of Ca2+ fluxes in oxidative cell death

Oxidative DNA damage to cells activates poly(ADP-ribose)polymerase-1 (PARP-1) and the poly(ADP-ribose) formed is rapidly degraded to ADP-ribose by poly(ADP-ribose)glycohydrolase (PARG). Here we show that PARP-1 and PARG control extracellular Ca(2+) fluxes through melastatin-like transient receptor potential 2 channels (TRPM2) in a cell death signaling pathway. TRPM2 activation accounts for essentially the entire Ca(2+) influx into the cytosol, activating caspases and causing the translocation of apoptosis inducing factor (AIF) from the inner mitochondrial membrane to the nucleus followed by cell death. Abrogation of PARP-1 or PARG function disrupts these signals and reduces cell death. ADP-ribose-loading of cells induces Ca(2+) fluxes in the absence of oxidative damage, suggesting that ADP-ribose is the key metabolite of the PARP-1/PARG system regulating TRPM2. We conclude that PARP-1/PARG control a cell death signal pathway that operates between five different cell compartments and communicates via three types of chemical messengers: a nucleotide, a cation, and proteins
Transforming growth factor-ß-inducible early response gene 1 is a novel substrate for atypical protein kinase Cs

The protein kinase C (PKC) family of serine/threonine kinases consists of ten different isoforms grouped into three subfamilies, denoted classical, novel and atypical PKCs (aPKCs). The aPKCs, PKC?/? and PKC? serve important roles during development and in processes subverted in cancer such as cell and tissue polarity, cell proliferation, differentiation and apoptosis. In an effort to identify novel interaction partners for aPKCs, we performed a yeast two-hybrid screen with the regulatory domain of PKC?/? as bait and identified the Krüppel-like factors family protein TIEG1 as a putative interaction partner for PKC?/?. We confirmed the interaction of both aPKCs with TIEG1 in vitro and in cells, and found that both aPKCs phosphorylate the DNA-binding domain of TIEG1 on two critical residues. Interestingly, the aPKC-mediated phosphorylation of TIEG1 affected its DNA-binding activity, subnuclear localization and transactivation potential.Transforming growth factor-ß-inducible early response gene 1 is a novel substrate for atypical protein kinase C
Cytoskeleton-mediated templating of complex cellulose-scaffolded extracellular structure and its association with oikosins in the urochordate Oikopleura

Oriented cellulose deposition is critical to plant patterning and models suggest microtubules constrain cellulose synthase movements through the plasma membrane. Though widespread in plants, urochordates are the only animals that synthesize cellulose. We characterized the distinctive cellulose microfibril scaffold of the larvacean house and its interaction with house structural proteins (oikosins). Targeted disruption of cytoskeletal elements, secretory pathways, and plasma membrane organization, suggested a working model for templating extracellular cellulose microfibrils from animal cells that shows both convergence and differences to plant models. Specialized cortical F-actin arrays template microfibril orientation and glycosylphosphatidylinositol-anchored proteins in lipid rafts may act as scaffolding proteins in microfibril elongation. Microtubules deliver and maintain cellulose synthase complexes to specific cell membrane sites rather than orienting their movement through the membrane. Oikosins are incorporated into house compartments directly above their corresponding cellular field of expression and interact with the cellulose scaffold to a variable extent
Emerging Knowledge of Regulatory Roles of D-Amino Acids in Bacteria

The D-enantiomers of amino acids have been thought to have relatively minor functions in biological processes. While L-amino acids clearly predominate in nature, D-amino acids are sometimes found in proteins that are not synthesized by ribosomes, and D-Ala and D-Glu are routinely found in the peptidoglycan cell wall of bacteria. Here, we review recent findings showing that D-amino acids have previously unappreciated regulatory roles in the bacterial kingdom. Many diverse bacterial phyla synthesize and release D-amino acids, including D-Met and D-Leu, which were not previously known to be made. These noncanonical D-amino acids regulate cell wall remodeling in stationary phase and cause biofilm dispersal in aging bacterial communities. Elucidating the mechanisms by which D-amino acids govern cell wall remodeling and biofilm disassembly will undoubtedly reveal new paradigms for understanding how extracytoplasmic processes are regulated as well as lead to development of novel therapeutics
Altered expression of securin (Pttg1) and serpina3n in the auditory system of hearing-impaired Tff3-deficient mice

11 páginas, 5 figuras, 1 tabla.-- et al.-- El pdf del artículo es la versión post-print.[Introduction]: Tff3 peptide exerts important functions in\ud
cytoprotection and restitution of the gastrointestinal (GI)\ud
tract epithelia. Moreover, its presence in the rodent inner\ud
ear and involvement in the hearing process was demonstrated\ud
recently. However, its role in the auditory system\ud
still remains elusive. Our previous results showed a deterioration\ud
of hearing with age in Tff3-deficient animals.\ud
[Results]: Present detailed analysis of auditory brain stem\ud
response (ABR) measurements and immunohistochemical\ud
study of selected functional proteins indicated a normal\ud
function and phenotype of the cochlea in Tff3 mutants.\ud
However, a microarray-based screening of tissue derived\ud
from the auditory central nervous system revealed an\ud
alteration of securin (Pttg1) and serpina3n expression\ud
between wild-type and Tff3 knock-out animals. This\ud
was confirmed by qRT-PCR, immunostaining and western\ud
blots.This work was supported by Ciberned, MiCINN\ud
and Red de Terapia Célular de Castilla y León.Peer reviewe
The FN3 and BRCT motifs in the exomer component Chs5p define a conserved module that is necessary and sufficient for its function

El pdf del artículo es la versión pre-print.Chs5p is a component of the exomer, a coat complex required to transport the chitin synthase Chs3p from the trans-Golgi network to the plasma membrane. The Chs5p N-terminal region exhibits fibronectin type III (FN3) and BRCT domains. FN3 domains are present in proteins that mediate adhesion processes, whereas BRCT domains are involved in DNA repair. Several fungi-including Schizosaccharomyces pombe, which has no detectable amounts of chitin-have proteins similar to Chs5p. Here we show that the FN3 and BRCT motifs in Chs5p behave as a module that is necessary and sufficient for Chs5p localization and for cargo delivery. The N-terminal regions of S. cerevisiae Chs5p and S. pombe Cfr1p are interchangeable in terms of Golgi localization, but not in terms of exomer assembly, showing that the conserved function of this module is protein retention in this organelle and that the interaction between the exomer components is organism-specific. © 2010 Springer Basel AG.This work has been supported by grants BFU2007- 61866 from the CICYT and GR231 from the Junta de Castilla y León, Spain. NdL was supported by a fellowship from the Spanish Ministry of Science. RMG and PBS were supported by postgraduate I3P fellowships from the Spanish council of research (CSIC).Peer Reviewe
Stimulation of olfactory ensheathing cell motility enhances olfactory axon growth

Axons of primary olfactory neurons are intimately associated with olfactory ensheathing cells (OECs) from the olfactory epithelium until the final targeting of axons within the olfactory bulb. However, little is understood about the nature and role of interactions between OECs and axons during development of the olfactory nerve pathway. We have used high resolution time-lapse microscopy to examine the growth and interactions of olfactory axons and OECs in vitro. Transgenic mice expressing fluorescent reporters in primary olfactory axons (OMP-ZsGreen) and ensheathing cells (S100߭DsRed) enabled us to selectively analyse these cell types in explants of olfactory epithelium. We reveal here that rather than providing only a permissive substrate for axon growth, OECs play an active role in modulating the growth of pioneer olfactory axons. We show that the interactions between OECs and axons were dependent on lamellipodial waves on the shaft of OEC processes. The motility of OECs was mediated by GDNF, which stimulated cell migration and increased the apparent motility of the axons, whereas loss of OECs via laser ablation of the cells inhibited olfactory axon outgrowth. These results demonstrate that the migration of OECs strongly regulates the motility of axons and that stimulation of OEC motility enhances axon extension and growth cone activity.Griffith Sciences, Griffith Institute for Drug DiscoveryFull Tex
Sox4 mediates Tbx3 transcriptional regulation of the gap junction protein Cx43

Tbx3, a T-box transcription factor, regulates key steps in development of the heart and other organ systems. Here, we identify Sox4 as an interacting partner of Tbx3. Pull-down and nuclear retention assays verify this interaction and in situ hybridization reveals Tbx3 and Sox4 to co-localize extensively in the embryo including the atrioventricular and outflow tract cushion mesenchyme and a small area of interventricular myocardium. Tbx3, SOX4, and SOX2 ChIP data, identify a region in intron 1 of Gja1 bound by all tree proteins and subsequent ChIP experiments verify that this sequence is bound, in vivo, in the developing heart. In a luciferase reporter assay, this element displays a synergistic antagonistic response to co-transfection of Tbx3 and Sox4 and in vivo, in zebrafish, drives expression of a reporter in the heart, confirming its function as a cardiac enhancer. Mechanistically, we postulate that Sox4 is a mediator of Tbx3 transcriptional activity. [KEYWORDS: Amino Acid Sequence; Animals; COS Cells; Cercopithecus aethiops; Connexin 43/ genetics; Gene Expression Regulation; Humans; Male; Mice; Molecular Sequence Data; SOXC Transcription Factors/chemistry/ metabolism; T-Box Domain Proteins/ metabolism; Transcription, Genetic; Zebrafish]
The functional RNA domain 5BSL3.2 within the NS5B coding sequence influences hepatitis C virus IRESmediated translation.

6 páginas con ilustraciones.Hepatitis C virus (HCV) translation is mediated by an internal ribosome entry site (IRES) located at the 5’\ud
end of the genomic RNA. The 3’ untranslatable region (3’UTR) stimulates translation by the recruitment\ud
of protein factors that simultaneously bind to the 5’ end of the viral genome. This leads to the formation\ud
of a macromolecular complex with a closed loop conformation, similar to that described for the captranslated\ud
mRNAs. We previously demonstrated the existence of a long range RNA-RNA interaction\ud
involving subdomain IIId of the IRES region and the stem-loop 5BSL3.2 of the CRE element at the 3’\ud
end of the viral genome. The present study provides evidences that the enhancement of HCV IRESdependent\ud
translation mediated by the 3’UTR is negatively controlled by the CRE region in the human\ud
hepatoma cell lines Huh-7 and Hep-G2 in a time-dependent manner. Domain 5BSL3.2 is the major\ud
partner in this process. Mutations in this motif lead to an increase in IRES activity by up to 8-fold. These\ud
data support the existence of a functional high order structure in the HCV genome that involves two\ud
evolutionarily conserved RNA elements, domain IIId in the IRES and stem-loop 5BSL3.2 in the CRE\ud
region. This interaction could have a role in the circularisation of the viral genome.This work was supported by Grants BFU2009-08137 from\ud
the Spanish Ministerio de Innovacio´n y Ciencia, CTS-5077 from the\ud
Junta de Andalucı´a and FEDER funds from the EU to A.B–H. C.R-LPeer reviewe
MicroRNAs mediate metabolic stresses and angiogenesis

MicroRNAs are short endogenous RNA molecules that are able to regulate (mainly inhibiting) gene expression at the post-transcriptional level. The MicroRNA expression profile is cell-specific, but it is sensitive to perturbations produced by stresses and diseases. Endothelial cells subjected to metabolic stresses, such as calorie restriction, nutrients excess (glucose, cholesterol, lipids) and hypoxia may alter their functionality. This is predictive for the development of pathologies like atherosclerosis, diabetes, and hypertension. Moreover, cancer cells can activate a resting endothelium by secreting pro-angiogenic factors, in order to promote neoangiogenesis, which is essential for tumor growth. Endothelial altered phenotype is mirrored by altered mRNA, microRNA, and protein expression, with a microRNA being able to control pathways by regulating the expression of multiple mRNAs. In this review we will consider the involvement of microRNAs in modulating the response of endothelial cells to metabolic stresses and their role in promoting or halting angiogenesis
Myelin-associated proteins block the migration of olfactory ensheathing cells: an in vitro study using single cell tracking and traction force microscopy

Newly generated olfactory receptor axons grow from the peripheral to the central nervous system aided by olfactory ensheathing cells (OECs). Thus, OEC transplantation has emerged as a promising therapy for spinal cord injuries and for other neural diseases. However, these cells do not present a uniform population, but, instead, a functionally heterogeneous population that exhibits a variety of responses including adhesion, repulsion and crossover during cell-cell and cell-matrix interactions. Some studies report that the migratory properties of OECs are compromised by inhibitory molecules and potentiated by chemical gradients. Here, we demonstrated that rodent OECs express all the components of the Nogo Receptor complex and that their migration is blocked by Myelin. Next, we used cell tracking and traction force microscopy to analyze OEC migration and its mechanical properties over Myelin. Our data relate the absence of traction force of OEC with lower migratory capacity, which correlates with changes in the F-Actin cytoskeleton and focal adhesion distribution. Lastly, OEC traction force and migratory capacity is enhanced after cell incubation with the Nogo Receptor inhibitor NEP1-40
Molecular and functional heterogeneity of GABAergic synapses

Knowledge of the functional organization of the GABAergic system, the main inhibitory neurotransmitter system, in the CNS has increased remarkably in recent years. In particular, substantial progress has been made in elucidating the molecular mechanisms underlying the formation and plasticity of GABAergic synapses. Evidence available ascribes a key role to the cytoplasmic protein gephyrin to form a postsynaptic scaffold anchoring GABA(A) receptors along with other transmembrane proteins and signaling molecules in the postsynaptic density. However, the mechanisms of gephyrin scaffolding remain elusive, notably because gephyrin can auto-aggregate spontaneously and lacks PDZ protein interaction domains found in a majority of scaffolding proteins. In addition, the structural diversity of GABA(A) receptors, which are pentameric channels encoded by a large family of subunits, has been largely overlooked in these studies. Finally, the role of the dystrophin-glycoprotein complex, present in a subset of GABAergic synapses in cortical structures, remains ill-defined. In this review, we discuss recent results derived mainly from the analysis of mutant mice lacking a specific GABA(A) receptor subtype or a core protein of the GABAergic postsynaptic density (neuroligin-2, collybistin), highlighting the molecular diversity of GABAergic synapses and its relevance for brain plasticity and function. In addition, we discuss the contribution of the dystrophin-glycoprotein complex to the molecular and functional heterogeneity of GABAergic synapses
Identification of functional differences between recombinant human α and β cardiac myosin motors

The myosin isoform composition of the heart is\ud
dynamic in health and disease and has been shown to affect\ud
contractile velocity and force generation. While different\ud
mammalian species express different proportions of a and\ud
b myosin heavy chain, healthy human heart ventricles\ud
express these isoforms in a ratio of about 1:9 (a:b) while\ud
failing human ventricles express no detectable a-myosin.\ud
We report here fast-kinetic analysis of recombinant human\ud
a and b myosin heavy chain motor domains. This represents the ﬁrst such analysis of any human muscle myosin\ud
motor and the ﬁrst of a-myosin from any species. Our\ud
ﬁndings reveal substantial isoform differences in individual\ud
kinetic parameters, overall contractile character, and predicted cycle times. For these parameters, a-subfragment 1\ud
(S1) is far more similar to adult fast skeletal muscle myosin\ud
isoforms than to the slow b isoform despite 91% sequence\ud
identity between the motor domains of a- and b-myosin.\ud
Among the features that differentiate a- from b-S1: the\ud
ATP hydrolysis step of a-S1 is *ten-fold faster than b-S1,\ud
a-S1 exhibits *ﬁve-fold weaker actin afﬁnity than b-S1,\ud
and actin a-S1 exhibits rapid ADP release, which is > tenfold faster than ADP release for b-S1. Overall, the cycle\ud
times are ten-fold faster for a-S1 but the portion of time\ud
each myosin spends tightly bound to actin (the duty ratio)\ud
is similar. Sequence analysis points to regions that might\ud
underlie the basis for this ﬁnding
Mesenchymal stem cells and neural crest stem cells from adult bone marrow: characterization of their surprising similarities and differences

The generation of neuronal cells from stem cells obtained from adult bone marrow is of significant clinical interest in order to design new cell therapy protocols for several neurological disorders. The recent identification in adult bone marrow of stem cells derived from the neural crest stem cells (NCSC) might explain the neuronal phenotypic plasticity shown by bone marrow cells. However, little information is available about the nature of these cells compared to mesenchymal stem cells (MSC), including their similarities and differences. In this paper, using transcriptomic as well as proteomic technologies, we compared NCSC to MSC and stromal nestin-positive cells, all of them isolated from adult bone marrow. We demonstrated that the nestin-positive cell population, which was the first to be described as able to differentiate into functional neurons, was a mixed population of NCSC and MSC. More interestingly, we demonstrated that MSC shared with NCSC the same ability to truly differentiate into Tuj1-positive cells when co-cultivated with paraformaldehyde-fixed cerebellar granule neurons. Altogether, those results suggest that both NCSC and MSC can be considered as important tools for cellular therapies in order to replace neurons in various neurological diseases