194 research outputs found
Ultrastructural Features of Osteoclasts In Situ
The morphology of in situ osteoclasts on endocortical surfaces of the femoral midshaft was examined by scanning electron microscopy. Mice were perfusion fixed and bone marrow plugs were flushed out of femoral diaphyseal cylinders. The bones were split longitudinally and the endocortical surfaces examined. This method left on the bone surface most of the endosteal cells in their natural, in situ shape and position. Most of the bone surface was lined by contiguous bone lining cells covering resting bone surfaces, making a clear physical barrier between the bone and marrow compartments. On resorption surfaces, which were characterized by excavation cavities, osteoclasts were very polymorphic and spread on the bone surface, extending large pseudopods. The in vivo morphology of individual osteoclasts appears somewhat similar to that described by other investigators on calvaria surfaces and for isolated osteoclasts adherent to artificial substrates. In the resorption domains, osteoclasts appeared to be connected with adjacent osteoclasts, suggesting that the cells form a functional syncytium in resorption areas
Bone Lining Cells: Structure and Function
Bone lining cells (BLC\u27s) cover inactive (nonremodeling) bone surfaces, particularly evident in the adult skeleton. BLC\u27s are thinly extended over bone surfaces, have flat or slightly ovoid nuclei, connect to other BLC\u27s via gap junctions, and send cell processes into surface canaliculi. BLC\u27s can be induced to proliferate and differentiate into osteogenic cells and may represent a source of determined osteogenic precursors. BLC\u27s and other cells of the endosteal tissues may be an integral part of the marrow stromal system and have important functions in hematopoiesis, perhaps by controlling the inductive microenvironment. Because activation of bone remodeling occurs on inactive bone surfaces, BLC\u27s may be involved in the propagation of the activation signal that initiates bone resorption and bone remodeling. Evidence also suggests that BLC\u27s are important in the maintenance of the bone fluids and the fluxes of ions between the bone fluid and interstitial fluid compartments for mineral homeostasis
Do Parents Recognize Autistic Deviant Behavior Long before Diagnosis? Taking into Account Interaction Using Computational Methods
BACKGROUND: To assess whether taking into account interaction synchrony would help to better differentiate autism (AD) from intellectual disability (ID) and typical development (TD) in family home movies of infants aged less than 18 months, we used computational methods. METHODOLOGY AND PRINCIPAL FINDINGS: First, we analyzed interactive sequences extracted from home movies of children with AD (Nโ=โ15), ID (Nโ=โ12), or TD (Nโ=โ15) through the Infant and Caregiver Behavior Scale (ICBS). Second, discrete behaviors between baby (BB) and Care Giver (CG) co-occurring in less than 3 seconds were selected as single interactive patterns (or dyadic events) for analysis of the two directions of interaction (CGโBB and BBโCG) by group and semester. To do so, we used a Markov assumption, a Generalized Linear Mixed Model, and non negative matrix factorization. Compared to TD children, BBs with AD exhibit a growing deviant development of interactive patterns whereas those with ID rather show an initial delay of development. Parents of AD and ID do not differ very much from parents of TD when responding to their child. However, when initiating interaction, parents use more touching and regulation up behaviors as early as the first semester. CONCLUSION: When studying interactive patterns, deviant autistic behaviors appear before 18 months. Parents seem to feel the lack of interactive initiative and responsiveness of their babies and try to increasingly supply soliciting behaviors. Thus we stress that credence should be given to parents' intuition as they recognize, long before diagnosis, the pathological process through the interactive pattern with their child
Yeast Mitochondrial Biogenesis: A Role for the PUF RNA-Binding Protein Puf3p in mRNA Localization
The asymmetric localization of mRNA plays an important role in coordinating posttranscriptional events in eukaryotic cells. We investigated the peripheral mitochondrial localization of nuclear-encoded mRNAs (MLR) in various conditions in which the mRNA binding protein context and the translation efficiency were altered. We identified Puf3p, a Pumilio family RNA-binding protein, as the first trans-acting factor controlling the MLR phenomenon. This allowed the characterization of two classes of genes whose mRNAs are translated to the vicinity of mitochondria. Class I mRNAs (256 genes) have a Puf3p binding motif in their 3'UTR region and many of them have their MLR properties deeply affected by PUF3 deletion. Conversely, mutations in the Puf3p binding motif alter the mitochondrial localization of BCS1 mRNA. Class II mRNAs (224 genes) have no Puf3p binding site and their asymmetric localization is not affected by the absence of PUF3. In agreement with a co-translational import process, we observed that the presence of puromycin loosens the interactions between most of the MLR-mRNAs and mitochondria. Unexpectedly, cycloheximide, supposed to solidify translational complexes, turned out to destabilize a class of mRNA-mitochondria interactions. Classes I and II mRNAs, which are therefore transported to the mitochondria through different pathways, correlated with different functional modules. Indeed, Class I genes code principally for the assembly factors of respiratory chain complexes and the mitochondrial translation machinery (ribosomes and translation regulators). Class II genes encode proteins of the respiratory chain or proteins involved in metabolic pathways. Thus, MLR, which is intimately linked to translation control, and the activity of mRNA-binding proteins like Puf3p, may provide the conditions for a fine spatiotemporal control of mitochondrial protein import and mitochondrial protein complex assembly. This work therefore provides new openings for the global study of mitochondria biogenesis
Spatio-Temporal Dynamics of Yeast Mitochondrial Biogenesis: Transcriptional and Post-Transcriptional mRNA Oscillatory Modules
Examples of metabolic rhythms have recently emerged from studies of budding
yeast. High density microarray analyses have produced a remarkably detailed
picture of cycling gene expression that could be clustered according to
metabolic functions. We developed a model-based approach for the decomposition
of expression to analyze these data and to identify functional modules which,
expressed sequentially and periodically, contribute to the complex and intricate
mitochondrial architecture. This approach revealed that mitochondrial
spatio-temporal modules are expressed during periodic spikes and specific
cellular localizations, which cover the entire oscillatory period. For instance,
assembly factors (32 genes) and translation regulators (47 genes) are expressed
earlier than the components of the amino-acid synthesis pathways (31 genes). In
addition, we could correlate the expression modules identified with particular
post-transcriptional properties. Thus, mRNAs of modules expressed
โearlyโ are mostly translated in the vicinity of
mitochondria under the control of the Puf3p mRNA-binding protein. This last
spatio-temporal module concerns mostly mRNAs coding for basic elements of
mitochondrial construction: assembly and regulatory factors. Prediction that
unknown genes from this module code for important elements of mitochondrial
biogenesis is supported by experimental evidence. More generally, these
observations underscore the importance of post-transcriptional processes in
mitochondrial biogenesis, highlighting close connections between nuclear
transcription and cytoplasmic site-specific translation
The emotional component of Infant Directed-Speech: A cross-cultural study using machine learning
Backgrounds: Infant-directed speech (IDS) is part of an interactive loop that plays an important role in infantsโ cognitive and social development. The use of IDS is universal and is composed of linguistic and emotional components. However, whether the emotional component has similar acoustics characteristics has not been studied automatically. Methods: We performed a cross-cultural study using automatic social signal processing techniques (SSP) to compare IDS across languages. Our speech corpus consisted of audio-recorded vocalizations from parents during interactions with their infant between the ages of 4 and 18 months. It included 6 databases of five languages: English, French, Hebrew (two databases: mothers/fathers), Italian, and Brazilian Portuguese. We used an automatic classifier that exploits the acoustic characteristics of speech and machine learning methods (Support Vector Machines, SVM) to distinguish emotional IDS and non-emotional IDS. Results: Automated classification of emotional IDS was possible for all languages and speakers (father and mother). The uni-language condition (classifier trained and tested in the same language) produced moderate to excellent classification results, all of which were significantly different from chance (P < 1 ร 10โ10). More interestingly, the cross-over condition (IDS classifier trained in one language and tested in another language) produced classification results that were all significantly different from chance (P < 1 ร 10โ10). Conclusion: The automated classification of emotional and non-emotional components of IDS is possible based on the acoustic characteristics regardless of the language. The results found in the cross-over condition support the hypothesis that the emotional component shares similar acoustic characteristics across languages
Repression of Mitochondrial Translation, Respiration and a Metabolic Cycle-Regulated Gene, SLF1, by the Yeast Pumilio-Family Protein Puf3p
Synthesis and assembly of the mitochondrial oxidative phosphorylation (OXPHOS) system requires genes located both in the nuclear and mitochondrial genomes, but how gene expression is coordinated between these two compartments is not fully understood. One level of control is through regulated expression mitochondrial ribosomal proteins and other factors required for mitochondrial translation and OXPHOS assembly, which are all products of nuclear genes that are subsequently imported into mitochondria. Interestingly, this cadre of genes in budding yeast has in common a 3โฒ-UTR element that is bound by the Pumilio family protein, Puf3p, and is coordinately regulated under many conditions, including during the yeast metabolic cycle. Multiple functions have been assigned to Puf3p, including promoting mRNA degradation, localizing nucleus-encoded mitochondrial transcripts to the outer mitochondrial membrane, and facilitating mitochondria-cytoskeletal interactions and motility. Here we show that Puf3p has a general repressive effect on mitochondrial OXPHOS abundance, translation, and respiration that does not involve changes in overall mitochondrial biogenesis and largely independent of TORC1-mitochondrial signaling. We also identified the cytoplasmic translation factor Slf1p as yeast metabolic cycle-regulated gene that is repressed by Puf3p at the post-transcriptional level and promotes respiration and extension of yeast chronological life span when over-expressed. Altogether, these results should facilitate future studies on which of the many functions of Puf3p is most relevant for regulating mitochondrial gene expression and the role of nuclear-mitochondrial communication in aging and longevity
Comparative Analysis of mRNA Targets for Human PUF-Family Proteins Suggests Extensive Interaction with the miRNA Regulatory System
Genome-wide identification of mRNAs regulated by RNA-binding proteins is crucial to uncover post-transcriptional gene regulatory systems. The conserved PUF family RNA-binding proteins repress gene expression post-transcriptionally by binding to sequence elements in 3โฒ-UTRs of mRNAs. Despite their well-studied implications for development and neurogenesis in metazoa, the mammalian PUF family members are only poorly characterized and mRNA targets are largely unknown. We have systematically identified the mRNAs associated with the two human PUF proteins, PUM1 and PUM2, by the recovery of endogenously formed ribonucleoprotein complexes and the analysis of associated RNAs with DNA microarrays. A largely overlapping set comprised of hundreds of mRNAs were reproducibly associated with the paralogous PUM proteins, many of them encoding functionally related proteins. A characteristic PUF-binding motif was highly enriched among PUM bound messages and validated with RNA pull-down experiments. Moreover, PUF motifs as well as surrounding sequences exhibit higher conservation in PUM bound messages as opposed to transcripts that were not found to be associated, suggesting that PUM function may be modulated by other factors that bind conserved elements. Strikingly, we found that PUF motifs are enriched around predicted miRNA binding sites and that high-confidence miRNA binding sites are significantly enriched in the 3โฒ-UTRs of experimentally determined PUM1 and PUM2 targets, strongly suggesting an interaction of human PUM proteins with the miRNA regulatory system. Our work suggests extensive connections between the RBP and miRNA post-transcriptional regulatory systems and provides a framework for deciphering the molecular mechanism by which PUF proteins regulate their target mRNAs
Trace elements in hemodialysis patients: a systematic review and meta-analysis
<p>Abstract</p> <p>Background</p> <p>Hemodialysis patients are at risk for deficiency of essential trace elements and excess of toxic trace elements, both of which can affect health. We conducted a systematic review to summarize existing literature on trace element status in hemodialysis patients.</p> <p>Methods</p> <p>All studies which reported relevant data for chronic hemodialysis patients and a healthy control population were eligible, regardless of language or publication status. We included studies which measured at least one of the following elements in whole blood, serum, or plasma: antimony, arsenic, boron, cadmium, chromium, cobalt, copper, fluorine, iodine, lead, manganese, mercury, molybdenum, nickel, selenium, tellurium, thallium, vanadium, and zinc. We calculated differences between hemodialysis patients and controls using the differences in mean trace element level, divided by the pooled standard deviation.</p> <p>Results</p> <p>We identified 128 eligible studies. Available data suggested that levels of cadmium, chromium, copper, lead, and vanadium were higher and that levels of selenium, zinc and manganese were lower in hemodialysis patients, compared with controls. Pooled standard mean differences exceeded 0.8 standard deviation units (a large difference) higher than controls for cadmium, chromium, vanadium, and lower than controls for selenium, zinc, and manganese. No studies reported data on antimony, iodine, tellurium, and thallium concentrations.</p> <p>Conclusion</p> <p>Average blood levels of biologically important trace elements were substantially different in hemodialysis patients, compared with healthy controls. Since both deficiency and excess of trace elements are potentially harmful yet amenable to therapy, the hypothesis that trace element status influences the risk of adverse clinical outcomes is worthy of investigation.</p
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