We report the differentiation of neural stem and progenitor cells solely induced by direct current (DC) pulses stimulation. Neural stem and progenitor cells in the adult mammalian brain are promising ...candidates for the development of therapeutic neuroregeneration strategies. The differentiation of neural stem and progenitor cells depends on various in vivo environmental factors, such as nerve growth factor and endogenous EF. In this study, we demonstrated that the morphologic and phenotypic changes of mouse neural stem and progenitor cells (mNPCs) could be induced solely by exposure to square-wave DC pulses (magnitude 300 mV/mm at frequency of 100-Hz). The DC pulse stimulation was conducted for 48 h, and the morphologic changes of mNPCs were monitored continuously. The length of primary processes and the amount of branching significantly increased after stimulation by DC pulses for 48 h. After DC pulse treatment, the mNPCs differentiated into neurons, astrocytes, and oligodendrocytes simultaneously in stem cell maintenance medium. Our results suggest that simple DC pulse treatment could control the fate of NPCs. With further studies, DC pulses may be applied to manipulate NPC differentiation and may be used for the development of therapeutic strategies that employ NPCs to treat nervous system disorders.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Centriole duplication involves the growing of a procentriole (progeny centriole) next to the proximal end of each pre-existing centriole (parental centriole). The molecular mechanisms that regulate ...procentriole elongation remain obscure. We show here that expression of the centriolar protein CPAP (centrosomal P4.1-associated protein) is carefully regulated during the cell cycle, with the protein being degraded in late mitosis. Depletion of CPAP inhibited centrosome duplication, whereas excess CPAP induced the formation of elongated procentriole-like structures (PLSs), which contain stable microtubules and several centriolar proteins. Ultrastructural analysis revealed that these structures are similar to procentrioles with elongated microtubules. Overexpression of a CPAP mutant (CPAP-377EE) that does not bind to tubulin dimers significantly inhibited the formation of CPAP-induced PLSs. Together, these results suggest that CPAP is a new regulator of centriole length and its intrinsic tubulin-dimer binding activity is required for procentriole elongation.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Centrioles are cylindrical structures that are usually composed of nine triplets of microtubules (MTs) organized around a cartwheel‐shaped structure. Recent studies have proposed a structural model ...of the SAS‐6‐based cartwheel, yet we do not know the molecular detail of how the cartwheel participates in centriolar MT assembly. In this study, we demonstrate that the human microcephaly protein, CEP135, directly interacts with hSAS‐6 via its carboxyl‐terminus and with MTs via its amino‐terminus. Unexpectedly, CEP135 also interacts with another microcephaly protein CPAP via its amino terminal domain. Depletion of CEP135 not only perturbed the centriolar localization of CPAP, but also blocked CPAP‐induced centriole elongation. Furthermore, CEP135 depletion led to abnormal centriole structures with altered numbers of MT triplets and shorter centrioles. Overexpression of a CEP135 mutant lacking the proper interaction with hSAS‐6 had a dominant‐negative effect on centriole assembly. We propose that CEP135 may serve as a linker protein that directly connects the central hub protein, hSAS‐6, to the outer MTs, and suggest that this interaction stabilizes the proper cartwheel structure for further CPAP‐mediated centriole elongation.
Different organism‐dependent centriole biogenesis roles have been suggested for CEP135/Bld10. Analysis of the human homologue CEP135/MCPH8 supports a key role in connecting the centriolar cartwheel hub SAS‐6, the elongation factor CPAP, and outer microtubules.
A common theme in the self-organization of multicellular tissues is the use of cell-cell signaling networks to induce morphological changes. We used the modular synNotch juxtacrine signaling platform ...to engineer artificial genetic programs in which specific cell-cell contacts induced changes in cadherin cell adhesion. Despite their simplicity, these minimal intercellular programs were sufficient to yield assemblies with hallmarks of natural developmental systems: robust self-organization into multidomain structures, well-choreographed sequential assembly, cell type divergence, symmetry breaking, and the capacity for regeneration upon injury. The ability of these networks to drive complex structure formation illustrates the power of interlinking cell signaling with cell sorting: Signal-induced spatial reorganization alters the local signals received by each cell, resulting in iterative cycles of cell fate branching. These results provide insights into the evolution of multicellularity and demonstrate the potential to engineer customized self-organizing tissues or materials.
In response to the globally escalating number of language learners tasked with learning science through a foreign language, this review seeks to bring new perspectives by reframing research findings, ...still dominated by historical language assumptions, through a contemporary language lens. We aim to unearth, amalgamate and expose the potentials of non-linguistic modes described by the theory of multiliteracies that appear sporadic and fragmentary within studies due to their linguistic focus, as we surmise they offer language learners alternative avenues for meaning-making. 40 peer-reviewed empirical studies published between 1995 and 2019 were systematically found and examined using theoretical thematic analysis to expand our understandings. We conjectured findings that appeared contingent upon non-linguistic modes but did not prominently feature in the reported results. In doing so, we used a multimodal and translanguaging lens from which three themes and educational implications emerged. The integration of non-linguistic modes in science: (1) aided language learners' science discourse, provided they had access to multiple modes and agency over expression; (2) facilitated multicultural learning communities validating each learner as a sense maker; and (3) promoted authentic and equitable learning experiences. Other noteworthy findings, such as the influence of the tactile mode, are discussed. Recommendations to future researchers include adopting epistemologies of language fitting to our century and developing transdisciplinary approaches to research.
Insomnia is prevalent, causing severe distress and impairment. This review focuses on illuminating the puzzling finding that many insomnia patients misperceive their sleep. They overestimate their ...sleep onset latency (SOL) and underestimate their total sleep time (TST), relative to objective measures. This tendency is ubiquitous (although not universal). Resolving this puzzle has clinical, theoretical, and public health importance. There are implications for assessment, definition, and treatment. Moreover, solving the puzzle creates an opportunity for real-world applications of theories from clinical, perceptual, and social psychology as well as neuroscience. Herein we evaluate 13 possible resolutions to the puzzle. Specifically, we consider the possible contribution, to misperception, of (1) features inherent to the context of sleep (e.g., darkness); (2) the definition of sleep onset, which may lack sensitivity for insomnia patients; (3) insomnia being an exaggerated sleep complaint; (4) psychological distress causing magnification; (5) a deficit in time estimation ability; (6) sleep being misperceived as wake; (7) worry and selective attention toward sleep-related threats; (8) a memory bias influenced by current symptoms and emotions, a confirmation bias/belief bias, or a recall bias linked to the intensity/recency of symptoms; (9) heightened physiological arousal; (10) elevated cortical arousal; (11) the presence of brief awakenings; (12) a fault in neuronal circuitry; and (13) there being 2 insomnia subtypes (one with and one without misperception). The best supported resolutions were misperception of sleep as wake, worry, and brief awakenings. A deficit in time estimation ability was not supported. We conclude by proposing several integrative solutions.
Mutations in many centriolar protein-encoding genes cause primary microcephaly. Using super-resolution and electron microscopy, we find that the human microcephaly protein, RTTN, is recruited to the ...proximal end of the procentriole at early S phase, and is located at the inner luminal walls of centrioles. Further studies demonstrate that RTTN directly interacts with STIL and acts downstream of STIL-mediated centriole assembly. CRISPR/Cas9-mediated RTTN gene knockout in p53-deficient cells induce amplification of primitive procentriole bodies that lack the distal-half centriolar proteins, POC5 and POC1B. Additional analyses show that RTTN serves as an upstream effector of CEP295, which mediates the loading of POC1B and POC5 to the distal-half centrioles. Interestingly, the naturally occurring microcephaly-associated mutant, RTTN (A578P), shows a low affinity for STIL binding and blocks centriole assembly. These findings reveal that RTTN contributes to building full-length centrioles and illuminate the molecular mechanism through which the RTTN (A578P) mutation causes primary microcephaly.Mutations in many centriolar protein-encoding genes cause primary microcephaly. Here the authors show that human microcephaly protein RTTN directly interacts with STIL and acts downstream of STIL-mediated centriole assembly, contributing to building full-length centrioles.
Centrioles duplicate only once per cell cycle in proliferating cells, whereas in multiciliated cells, hundreds of centrioles form almost simultaneously. The molecular control mechanisms that govern ...centriole amplification in multiciliated cells are largely unknown. Two studies highlight Deup1 and CCDC78 as key players in this process.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
We report the updated classification of primary immunodeficiencies compiled by the Primary Immunodeficiency Expert Committee (PID EC) of the International Union of Immunological Societies (IUIS). In ...the two years since the previous version, 34 new gene defects are reported in this updated version. For each disorder, the key clinical and laboratory features are provided. In this new version we continue to see the increasing overlap between immunodeficiency, as manifested by infection and/or malignancy, and immune dysregulation, as manifested by auto-inflammation, auto-immunity, and/or allergy. There is also an increased number of genetic defects that lead to susceptibility to specific organisms which reflects the finely tuned nature of immune defense systems. This classification is the most up to date catalogue of all known and published primary immunodeficiencies and acts as a current reference of the knowledge of these conditions and is an important aid for the genetic and molecular diagnosis of patients with these rare diseases.
CPAP is required for centriole elongation during S/G2 phase, but the role of CPAP in mitosis is incompletely understood. Here, we show that CPAP maintains spindle pole integrity through its ...phosphorylation by Aurora-A during mitosis. Depletion of CPAP induced a prolonged delay in mitosis, pericentriolar material (PCM) dispersion, and multiple mitotic abnormalities. Further studies demonstrated that CPAP directly interacts with and is phosphorylated by Aurora-A at serine 467 during mitosis. Interestingly, the dispersal of the PCM was effectively rescued by ectopic expression of wild-type CPAP or a phospho-mimic CPAP-S467D mutant, but not a non-phosphorylated CPAP-S467A mutant. Finally, we found that CPAP-S467D has a low affinity for microtubule binding but a high affinity for PCM proteins. Together, our results support a model wherein CPAP is required for proper mitotic progression, and phosphorylation of CPAP by Aurora-A is essential for maintaining spindle pole integrity.
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•Depletion of CPAP induces multiple mitotic abnormalities•CPAP is phosphorylated by Aurora-A at Ser 467 during mitosis•Phosphorylated CPAP coheres PCM proteins and maintains centrosome integrity•Phosphorylated CPAP has a high affinity for PCM proteins but a low affinity for MTs
Chou et al. show that CPAP is essential for proper mitotic progression and maintenance of spindle pole integrity. CPAP is phosphorylated by Aurora-A during mitosis and phosphorylated CPAP coheres PCM proteins and maintains centrosome integrity.
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