Cytoplasmic messenger ribonucleoprotein particles (mRNPs) represent the cellular transcriptome, and recent data have challenged our current understanding of their architecture, transport, and complexity before translation. Pre‐translational mRNPs are composed of a single transcript, whereas P‐bodies and stress granules are condensates. Both pre‐translational mRNPs and actively translating mRNPs seem to adopt a linear rather than a closed‐loop configuration. Moreover, assembly of pre‐translational mRNPs in physical RNA regulons is an unlikely event, and co‐regulated translation may occur locally following extracellular cues. We (...) envisage a stochastic mRNP transport mechanism where translational repression of single mRNPs—in combination with microtubule‐mediated cytoplasmic streaming and docking events—are prerequisites for local translation, rather than direct transport. (shrink)

One of the relations used with granularity is indistinguishability, where distinguishable entities in a finer-grained granule are indistinguishable in a coarser-grained granule. This relation is a subtype of equivalence relation, which is used in the other direction to create finer-grained granules. Together with the notion of similarity, we formally prove some intuitive properties of the indistinguishability relation for both qualitative and quantitative granularity, that with a given granulation there must be at least two granules (levels of granularity) for (...) it to be granular, and derive a strict order between finer and coarser granules. Based on these results, granulation hierarchy is defined as extra assisting structure to augment implementations. (shrink)

In eukaryotes, the messenger RNA (mRNA), the blueprint of a protein‐coding gene, is processed and packaged into a messenger ribonucleoprotein particle (mRNP) by mRNA‐binding proteins in the nucleus. The steps of mRNP formation – transcription, processing, packaging, and the orchestrated release of the export‐competent mRNP from the site of transcription for nuclear mRNA export – are tightly coupled to ensure a highly efficient and regulated process. The importance of highly accurate nuclear mRNP formation is illustrated by (...) the fact that mutations in components of this pathway lead to cellular inviability or to severe diseases in metazoans. We hypothesize that efficient mRNP formation is realized by a molecular mRNP packaging station, which is built by several recruitment platforms and coordinates the individual steps of mRNP formation. (shrink)

A novel data-driven model-free adaptive control approach is first proposed by combining the advantages of model-free adaptive control and data-driven optimal iterative learning control, and then its stability and convergence analysis is given to prove algorithm stability and asymptotical convergence of tracking error. Besides, the parameters of presented approach are adaptively adjusted with fuzzy logic to determine the occupied proportions of MFAC and DDOILC according to their different control performances in different control stages. Lastly, the proposed fuzzy DDMFAC approach is (...) applied to the control of particle quality in drug development phase of spray fluidized-bed granulation process, and its control effect is compared with MFAC and DDOILC and their fuzzy forms, in which the parameters of MFAC and DDOILC are adaptively adjusted with fuzzy logic. The effectiveness of the presented FDDMFAC approach is verified by a series of simulations. (shrink)

© 2015 Elsevier Inc.Toxoplasma gondii is a protozoan pathogen in the phylum Apicomplexa that resides within an intracellular parasitophorous vacuole that is selectively permeable to small molecules through unidentified mechanisms. We have identified GRA17 as a Toxoplasma-secreted protein that localizes to the parasitophorous vacuole membrane and mediates passive transport of small molecules across the PVM. GRA17 is related to the putative Plasmodium translocon protein EXP2 and conserved across PV-residing Apicomplexa. The PVs of GRA17-deficient parasites have aberrant morphology, reduced permeability to (...) small molecules, and structural instability. GRA17-deficient parasites proliferate slowly and are avirulent in mice. These GRA17-deficient phenotypes are rescued by complementation with Plasmodium EXP2. GRA17 functions synergistically with a related protein, GRA23. Exogenous expression of GRA17 or GRA23 alters the membrane conductance properties of Xenopus oocytes in a manner consistent with a large non-selective pore. Thus, GRA17 and GRA23 provide a molecular basis for PVM permeability and nutrient access. (shrink)

It is now clear that two prominent nuclear domains, interchromatin granule clusters (IGCs) and Cajal bodies (CBs), contribute to the highly ordered organization of the extrachromosomal space of the cell nucleus. These functional domains represent structurally stable but highly dynamic nuclear organelles enriched in factors that are required for different nuclear activities, especially RNA biogenesis. IGCs are considered to be the main sites for storage, assembly, and/or recycling of the essential spliceosome components. CBs are involved in the biogenesis of several (...) classes of small RNPs as well as the modification of newly assembled small nuclear RNA. We have summarized data on the molecular composition, structure, and functional roles of IGCs and CBs in the nuclei of mammalian somatic cells and oocytes of some animals with a special focus on insects. We have focused on similarities and differences between the IGCs and CBs of oocytes and the well‐studied CBs and IGCs of cultured mammalian somatic cells. We have shown the heterogeneous character of oocyte IGCs and CBs, both in structure and molecular content. We have also demonstrated the unique capacity of oocytes to form close structural interactions between IGC and CB components. We proposed to consider these joint structures as integrated entities, sharing the features of both IGCs and CBs. (shrink)

Regulated secretory proteins are stored within specialized vesicles known as secretory granules. It is not known how proteins are sorted into these organelles. Regulated proteins may possess targeting signals which interact with specific sorting receptors in the lumen of the trans‐Golgi network (TGN) prior to their aggregation to form the characteristic dense‐core of the granule. Alternatively, sorting may occur as the result of specific aggregation of regulated proteins in the TGN. Aggregates may be directed to secretory granules by (...) interaction of a targeting signal on the surface with a sorting receptor. Novel targeting signals which confer on regulated proteins a tendency to aggregate under certain conditions, and in so doing cause them to be incorporated into secretory granules, have been implicated. Specific targeting signals may also play a role in directing membrane proteins to secretory granules. (shrink)

Electron microscopic examination of the non‐granulated cells of the adenohypophysis of several species has evidenced a unity of structure amongst vertebrates. Efforts to correlate structure and function have been made, but they have often been hampered by the scarcity or absence of direct experimental methods for the investigation of their function. Yet often the evidence in favor of a given role has been circumstantial, relying on coincidences between changes in the secretory activity of the gland and changes in the ultrastructure (...) of the non‐granulated cells or in colloid production. At the present time, the prevailing hypothesis is that, in addition to a possible role in mechanical support within the gland, the non‐granulated cells seem to be important with respect to the secretory process of the endocrine cells and/or to the metabolism of the adenohypophysis. (shrink)

We present techniques for integrating low‐level neurobiological constraints into high‐level, functional cognitive models. In particular, we use these techniques to construct a model of eyeblink conditioning in the cerebellum based on temporal representations in the recurrent Granule‐Golgi microcircuit.

We introduce an abstract framework for general rough set theory from a mereological perspective and consider possible concepts of ’a priori’ granules and granulation in the same. The framework is ideal for relaxing many of the relatively superfluous set-theoretic axioms and for improving the semantics of many relation based, cover-based and dialectical rough set theories. This is a relatively simplified presentation of a section in three different recent research papers by the present author.

Six years ago, the Singer lab published a landmark paper which described how individual mRNA particles cross the nuclear pore complex in mammalian tissue culture cells. This involved the simultaneous imaging of mRNAs, each labeled by a large number of tethered fluorescent proteins and fluorescently tagged nuclear pore components. Now two groups have applied this technique to the budding yeast Saccharomyces cerevisiae. Their results indicate that in the course of nuclear export, mRNAs likely engage complexes that are present on either (...) side of the pore and that these interactions are modulated by proteins present in the messenger ribonucleoprotein (mRNP) complex. These findings lend support to the notion that just before and/or after the completion of nuclear export, mRNPs undergo one or more maturation steps that prepare the packaged mRNAs for translation. These results represent new and exciting insights into the mechanism of mRNA nuclear export. (shrink)

The germ track is the cellular path by which genes are transmitted to future generations whereas somatic cells die with their body and do not leave direct descendants. Transposable elements (TEs) evolve to be silent in somatic cells but active in the germ track. Thus, the performance of most bodily functions by a sequestered soma reduces organismal costs of TEs. Flexible forms of gene regulation are permissible in the soma because of the self‐imposed silence of TEs, but strict licensing of (...) transcription and translation is maintained in the germ track to control proliferation of TEs. Delayed zygotic genome activation (ZGA) and maternally inherited germ granules are adaptations that enhance germ‐track security. Mammalian embryos exhibit very early ZGA associated with extensive mobilization of retroelements. This window of vulnerability to retrotransposition in early embryos is an indirect consequence of evolutionary conflicts within the mammalian genome over postzygotic maternal provisioning. (shrink)

Random-excitation granule cells are likely to overwhelm spatiotemporal sequences described as in Braitenberg et al.'s target article. A mechanism is proposed involving the Golgi cells to reinforce tidal waves against noise. The recurrent inhibition by the Golgi calls can recruit random excitations of granule cells in phase with sequences of mossy fiber input.

Between 1905 and 1913, French physicist Jean Perrin's experiments on Brownian motion ostensibly put a definitive end to the long debate regarding the real existence of molecules, proving the atomic theory of matter. While Perrin's results had a significant impact at the time, later examination of his experiments questioned whether he really gained experimental access to the molecular realm. The experiments were successful in determining the mean kinetic energy of the granules of Brownian motion; however, the values for molecular (...) magnitudes Perrin inferred from them simply presupposed that the granule mean kinetic energy was the same as the mean molecular kinetic energy in the fluid in which the granules move. This stipulation became increasingly questionable in the years between 1908 and 1913, as significantly lower values for these magnitudes were obtained from other experimental results like alpha-particle emissions, ionization, and Planck's blackbody radiation equation. In this case study in the history and philosophy of science, George E. Smith and Raghav Seth here argue that despite doubts, Perrin's measurements were nevertheless exemplars of theory-mediated measurement-the practice of obtaining values for an inaccessible quantity by inferring them from an accessible proxy via theoretical relationships between them. They argue that it was actually Perrin more than any of his contemporaries who championed this approach during the years in question. The practice of theory-mediated measurement in physics had a long history before 1900, but the concerted efforts of Perrin, Rutherford, Millikan, Planck, and their colleagues led to the central role this form of evidence has had in microphysical research ever since. Seth and Smith's study thus replaces an untenable legend with an account that is not only tenable, but more instructive about what the evidence did and did not show. (shrink)

Recent findings indicate that substantial cross‐talk may exist between transcriptional and post‐transcriptional processes. Firstly, there are suggestions that specific promoters influence the post‐transcriptional fate of transcripts, pointing to communication between protein complexes assembled on DNA and nascent pre‐mRNA. Secondly, an increasing number of proteins appear to be multifunctional, participating in transcriptional and post‐transcriptional events. The classic example is TFIIIA, required for both the transcription of 5S rRNA genes and the packaging of 5S rRNA. TFIIIA is now joined by the Y‐box (...) proteins, which bind DNA (transcription activation and repression) and RNA (mRNA packaging). Furthermore, the tumour suppressor WT1, at first thought to be a typical transcription factor, may also be involved in splicing; conversely, hnRNP K, a bona fide pre‐mRNA‐binding protein, appears to be a transcription factor. Other examples of multifunctional proteins are mentioned: notably PTB, Sxl, La and PU.1. It is now reasonable to assert that some proteins, which were first identified as transcription factors, could just as easily have been identified as splicing factors, hnRNP, mRNP proteins and vice versa. It is no longer appropriate to view gene expression as a series of compartmentalised processes; instead, multifunctional proteins are likely to co‐ordinate different steps of gene expression. (shrink)

With the rapidly growing amounts of information, visualization is becoming increasingly important, as it allows users to easily explore and understand large amounts of information. However the field of information visualiza- tion currently lacks sufficient theoretical foundations. This article addresses foundational questions connecting information visualization with computing and philosophy studies. The idea of multiscale information granula- tion is described based on two fundamental concepts: information (structure) and computation (process). A new information processing paradigm of Granular Computing enables stepwise increase of (...) granulation/aggregation of information on different levels of resolution, which makes possible dynamical viewing of data. Information produced by Google Earth is an illustration of visualization based on clustering (granulation) of information on a succession of layers. Depending on level, specific emergent properties become visible as a result of different ways of aggregation of data/information. As information visualization ultimately aims at amplifying cognition, we discuss the process of simulation and emulation in relation to cognition, and in particular visual cognition. (shrink)

Braitenberg et al.'s proposal, like most previous theories of cerebellar function (see Bower 1997, for review), is fundamentally based on the striking geometric relationship between parallel fibers and Purkinje cells. As in previous models, the current theory assumes that the activation of granule cells results in a of activated Purkinje cells, although it adds the new requirement that the granule cell layer itself have a particular spatial/temporal pattern of activation. I believe there is clear evidence that parallel fibers do not (...) have the type of excitatory effects on Purkinje cells required by this theory. (shrink)

The eyespot organelle of the green alga Chlamydomonas allows the cell to phototax toward (or away) from light to maximize the light intensity for photosynthesis and minimize photo‐damage. At cytokinesis, the eyespot is resorbed at the cleavage furrow and two new eyespots form in the daughter cells 180° from each other. The eyespots are positioned asymmetrically with respect to the microtubule cytoskeleton. Eyespots are assembled from all three chloroplast membranes and carotenoid‐filled granules, which form a sandwich structure overlaid by (...) the tightly apposed plasma membrane. This review describes (1) my interest in cellular asymmetry and organelle biology, (2) isolation of mutations that describe four genes governing eyespot placement and assembly, (3) the characterization of the EYE2 gene, which encodes a thioredoxin superfamily member, and (4) the characterization of the MIN1 gene, which is required for the layered organization of granules and membranes in the eyespot. BioEssays 25:410–416, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

Protein secretion is conventionally viewed as taking place by either of two cellular routes, a regulated pathway, involving external stimuli and secretory granules, and a presumptive ‘constitutive’ pathway, which does not involve hormonal or neuronal stimuli or the production of secretory granules. The evidence reviewed here strongly suggests that there are post‐synthesis rate‐limiting steps for many proteins released by the ‘constitutive’ pathway and, hence, that regulation in some sense is involved here too. The nature of these rate‐limiting determinants (...) and events is discussed. (shrink)

Neurons are now known to produce a variety of types of chemical transmitters. Classical transmitters are stored within synaptic vesicles which undergo synaptic exocytosis in association with presynaptic thickenings. The larger, dense‐cored secretory granules present in most neurons contain neuropeptides and mainly discharge their contents at morphologically undifferentiated (i.e.nonsynaptic) sites. The synaptic character of vesicle discharge enables transmitters to exercise a highly focal action, whereas nonsynaptic release probably relates to the slow rate of degradation of many neuropeptides and their (...) consequent widespread diffusion and sphere of action. However, one variant of the basic pattern, involving the restriction of granule discharge to areas of the terminal plasmalemma situated adjacent to the postsynaptic cells (i.e. a parasynaptic configuration), enables a degree of targeted peptide discharge to be achieved. The diversity of patterns of neural exocytosis adds a further dimension to the complexity of nervous function. (shrink)

Apoptosis‐inducing factor (AIF) is expelled from mitochondria after some apoptotic stimuli and translocates to the nucleus, which may contribute to DNA and nuclear fragmentation in some non‐physiological mammalian cell deaths. Conversely, the requirement for mitochondrial AIF in oxidative phosphorylation and energy generation provides a plausible explanation for the embryonic lethality or neurodegeneration that has been found in different AIF‐deficient mouse models. These findings may help illuminate the ability of mitochondrial AIF to suppress cytoplasmic stress granule formation and to promote the (...) tumorigenic growth of cancer cells. AIF is ideally located in the mitochondrion to perform a vital normal function in energy production. Once it translocates to the nucleus, however, the cell might die either of energy failure or nuclear fragmentation (or both). We propose that the main function of AIF is to support energy production in both normal and transformed cell physiology, whereas nuclear‐translocated AIF might contribute to stress‐induced or pathological cell death in certain scenarios. BioEssays 28: 834–843, 2006. © 2006 Wiley Periodicals, Inc. (shrink)

Permeabilized cell models provide an experimental middle ground wherein the in vitro properties of mechanochemical proteins can be reconciled with the physical and topological constraints of the intact cell. Several well‐studied examples of organelle motility are described here, including the actin‐based cytoplasmic streaming of Characean algae, the microtubule‐based aggregation and dispersion of pigment granules in chromatophores and the saltatory movements of vesicles along microtubules in fibroblasts and macrophages. The permeabilized models developed for these systems have helped to integrate observations (...) in vivo with in vitro assays of motor proteins. (shrink)

Where the isocortex comes from is an important question, but even more important is understanding what it leads to – that is, what advantage is afforded by its peculiar organization in layers of distinct neuronal types. A computational hypothesis accounts for granulation and for the differentiation between supra- and infragranular pyramidal layers, as quantitatively advantageous to support fine topography in sensory maps.

Interest in the role of nitric oxide (NO) in the nervous system began with the demonstration that glutamate receptor activation in cerebellar slices causes the formation of a diffusible messenger with properties similar to those of the endothelium-derived relaxing factor. It is now clear that this is due to the Ca2+/calmodulin-dependent activation of the enzyme NO synthase, which forms NO and citrulline from the amino acid L-arginine. The cerebellum has very high levels of NO synthase, and although it has low (...) levels of guanylyl cyclase, cerebellar cyclic guanosine monophosphate (cGMP) levels are an order of magnitude higher than in other brain regions. A transcellular metabolic pathway is also present in the cerebellar cortex to recycle citrulline back to arginine. The NO formed binds to and activates soluble guanylyl cyclase to elevate cGMP levels in target cells. Studies employing NADPH-diaphorase, a selective histochemical marker for NO synthase, together with immunohistochemistry, in situ hybridization and biochemical studies have indicated that NO production occurs in granule and basket cells in the cerebellar cortex, whereas cGMP formation appears to occur largely in other cells, including Purkinje cells. Given that a long-term depression of AMPA currents can be seen in isolated Purkinje cells, this anatomical localization suggests that NO cannot play an essential role in the induction of this form of synaptic plasticity. (shrink)

Rough set theory has been successfully applied to many fields, such as data mining, pattern recognition, and machine learning. Kernel rough sets and neighborhood rough sets are two important models that differ in terms of granulation. The kernel rough sets model, which has fuzziness, is susceptible to noise in the decision system. The neighborhood rough sets model can handle noisy data well but cannot describe the fuzziness of the samples. In this study, we define a novel model called kernel neighborhood (...) rough sets, which integrates the advantages of the neighborhood and kernel models. Moreover, the model is used in the problem of feature selection. The proposed method is tested on the UCI datasets. The results show that our model outperforms classic models. (shrink)

The rapid dynamics of COVID-19 calls for quick and effective tracking of virus transmission chains and early detection of outbreaks, especially in the “phase 2” of the pandemic, when lockdown and other restriction measures are progressively withdrawn, in order to avoid or minimize contagion resurgence. For this purpose, contact-tracing apps are being proposed for large scale adoption by many countries. A centralized approach, where data sensed by the app are all sent to a nation-wide server, raises concerns about citizens’ privacy (...) and needlessly strong digital surveillance, thus alerting us to the need to minimize personal data collection and avoiding location tracking. We advocate the conceptual advantage of a decentralized approach, where both contact and location data are collected exclusively in individual citizens’ “personal data stores”, to be shared separately and selectively, voluntarily, only when the citizen has tested positive for COVID-19, and with a privacy preserving level of granularity. This approach better protects the personal sphere of citizens and affords multiple benefits: it allows for detailed information gathering for infected people in a privacy-preserving fashion; and, in turn this enables both contact tracing, and, the early detection of outbreak hotspots on more finely-granulated geographic scale. The decentralized approach is also scalable to large populations, in that only the data of positive patients need be handled at a central level. Our recommendation is two-fold. First to extend existing decentralized architectures with a light touch, in order to manage the collection of location data locally on the device, and allow the user to share spatio-temporal aggregates—if and when they want and for specific aims—with health authorities, for instance. Second, we favour a longer-term pursuit of realizing a Personal Data Store vision, giving users the opportunity to contribute to collective good in the measure they want, enhancing self-awareness, and cultivating collective efforts for rebuilding society. (shrink)

Adequate reprogramming of cellular metabolism in response to stresses or suboptimal growth conditions involves a myriad of coordinated changes that serve to promote cell survival. As protein synthesis is an energetically expensive process, its regulation under stress is of critical importance. Reprogramming of messenger RNA (mRNA) translation involves well‐understood stress‐activated kinases that target components of translation initiation machinery, resulting in the robust inhibition of general translation and promotion of the translation of stress‐responsive proteins. Translational arrest of mRNAs also results in (...) the accumulation of transcripts in cytoplasmic foci called stress granules. Recent studies focus on the key roles of transfer RNA (tRNA) in stress‐induced translational reprogramming. These include stress‐specific regulation of tRNA pools, codon‐biased translation influenced by tRNA modifications, tRNA miscoding, and tRNA cleavage. In combination, signal transduction pathways and tRNA metabolism changes regulate translation during stress, resulting in adaptation and cell survival. This review examines molecular mechanisms that regulate protein synthesis in response to stress. (shrink)

Two aspects of the chromatin repeat length (r t) are discussed: (i) Why is r t, longer for slowly dividing cells than in rapidly dividing cells?, and (ii) Why is the temporal evolution of r ta decreasing function of time (t) in mammalian cortical neurons, whereas it is an increasing function of t for granule cells around the time of birth? These questions are discussed in terms of a hypothesis which assumes a correlation between deoxyribonucleic acid (DNA) packaging, transcription, and (...) replication. (shrink)

The remodeling of biological membranes is crucial for a vast number of cellular activities and is an inherently multiscale process in both time and space. Seminal work has provided important insights into nanometer‐scale membrane deformations, and highlighted the remarkable variation and complexity in the underlying molecular machineries and mechanisms. However, how membranes are remodeled at the micron‐scale, particularly in vivo, remains poorly understood. Here, we discuss how using regulated exocytosis of large (1.5–2.0 μm) membrane‐bound secretory granules in the salivary (...) gland of live mice as a model system, has provided evidence for the importance of the actomyosin cytoskeleton in micron‐scale membrane remodeling in physiological conditions. We highlight some of these advances, and present mechanistic hypotheses for how the various biochemical and biophysical properties of distinct actomyosin networks may drive this process. (shrink)

El desarrollo acelerado de la ciencia y la técnica ha proporcionado nuevos conocimientos, entre ellos los relacionados con la biología molecular y celular y particularmente con el descubrimiento del factor de crecimiento epidérmico y su capacidad para estimular la formación de tejido de granulación y acelerar la reepitelización en las úlceras del pie diabético. Los Estudios Sociales de la Ciencia y la Tecnología constituyen un campo caracterizado por la heterogeneidad de tendencias que han ido configurando un enfoque más integral, interdisciplinario (...) y responsable de la reflexión sobre la actividad científico-tecnológica. El artículo tiene como objetivo fundamentar el impacto social del Heberprot-P como fruto de una Tecnociencia, mediante un análisis teórico del tema. The quick development of science and technology has provided new knowledge about different matters, such as those related with the molecular and cellular biology and particularly with the discovery of the factor of epidermal growth and its capacity to stimulate the formation of granulation tissue and to accelerate the re-epithelisation in ulcers of diabetic foot. The Social Studies of Science and Technology constitute a field characterized by heterogeneity of tendencies that have been giving shape to a more integral and interdisciplinary focus responsible for the reflection on the scientific-technological activity. This article is aimed at basing the social impact of Heberprot-P as a result of a technoscience, by means of a theoretical analysis on the topic. (shrink)

The two theories of pancreatic enzyme secretion, those of exocytosis and transmembrane flow, are described. Data thought to support the theory of transmembrane flow of single molecules from pancreatic acinar cells are first reviewed, and the conditions which could allow these data to be explained by the theory of exocytosis of enzyme quanta, i.e. secretory granules, are then discussed.The evidence suggesting short‐term modulation of the composition of pancreatic juice is also considered, and its possible explanations at the organ and (...) cellular level are discussed, in the light of suggested theories on enzyme secretion pathways. (shrink)

Cognitive deficits were produced in rats by different methods of damaging the brain: chronic ingestion of alcohol, causing widespread damage to diffuse cholinergic and aminergic projection systems; lesions (by local injection of the excitotoxins, ibotenate, quisqualate, and AMPA) of the nuclei of origin of the forebrain cholinergic projection system (FCPS), which innervates the neocortex and hippocampal formation; transient cerebral ischaemia, producing focal damage especially in the CA1 pyramidal cells of the dorsal hippocampus; and lesions (by local injection of the neurotoxin, (...) colchicine) of the granule cells of the dentate gyrus. Following chronic alcohol or lesions of the FCPS, transplants of cholinergically rich fetal brain tissue into the terminal areas (neocortex and/or hippocampus) restored performance almost to control levels, with a time course consistent with growth of the transplants and integration with host tissue; transplants of cholinergically poor fetal tissue (hippocampus) were without effect, as were transplants of cholinergically rich tissue into the region containing the nuclei of origin of the FCPS. Grafts of primary cells enriched in glia and cultured neuroblastoma cells into the terminal areas of the FCPS were equally effective, suggesting that there are multiple mechanisms by which neural transplants can restore cognitive function following diffuse cholinergic damage. In contrast, after ischaemia- or neurotoxin-induced damage to CA1 or dentate granule cells respectively, cholinergically rich fetal transplants into the damaged hippocampal formation were ineffective in restoring performance. After ischaemic damage, however, performance was restored by suspension grafts of CA1 cells but not by transplants containing CA3 pyramidal cells or granule cells; and after colchicine damage it was restored by solid grafts containing granule but not CA1 pyramidal cells. Furthermore, electrophysiological evidence has demonstrated functional, graft type-specific host-graft functional neuronal connectivity. Thus, restoration of cognitive function by neural transplants is possible after damage to either diffuse (cholinergic) or point-to-point (intrahippocampal) forebrain systems, but the transplant must be appropriate to the damage to be repaired. Because the different types of brain damage studied provide analogues of human alcoholic dementia, Alzheimer's disease, and heart attack, these results are encouraging with regard to the eventual application of neural transplant surgery to the treatment of cognitive deficits in humans. (shrink)

Conditions are stated under which the "argument by analogy" is consistent with the principle of inverse probability. It is contended that the argument by analogy, in conjunction with a crucial test, has a legitimate place in scientific logic. As an example the astrophysical problem of solar granulation is discussed in detail and other examples are mentioned more briefly.

In A. Kumar, & M. Banerjee [(2012). Definable and rough sets in covering-based approximation spaces. In T. Li. (eds.), Rough sets and knowledge technology (pp. 488–495). Springer-Verlag], A. Kumar, & M. Banerjee [(2015). Algebras of definable and rough sets in quasi order-based approximation spaces. Fundamenta Informaticae, 141(1), 37–55], authors proposed a pair of lower and upper approximation operators based on granules generated by quasiorders. This work is an extension of algebraic results presented therein. A characterisation has been presented for (...) those quasiorder-generated covering-based approximation spaces whose corresponding collections of definable and rough sets form Stone algebras. The notion of rough lattice was proposed in A. Kumar, & M. Banerjee [(2015). Algebras of definable and rough sets in quasi order-based approximation spaces. Fundamenta Informaticae, 141(1), 37–55], A. Kumar [(2020). A Study of Algebras and Logics of Rough Sets Based on Classical and Generalized Approximation Spaces. In Transactions on Rough Sets XXII, LNCS (Vol. 12485, pp. 123–251). Springer]. Some special rough lattices are introduced in this work, viz. rough Stone algebra, ∼1-complemented and ∼2-complemented rough lattices. Representations of these algebras in terms of rough sets are obtained. Moreover, logics for these algebras are shown to be sound and complete with respect to rough set semantics. (shrink)

Mammalian sperm undergo discharge of a single, anterior secretory granule following their attachment to the zona pellucida surrounding the oocyte. This secretory discharge is known for historical reasons as the acrosome reaction. It fulfils a number of purposes and without it, sperm are unable to penetrate the zona pellucida and fuse with the oocyte. In this review, we focus on the role of the acrosome reaction in the development of fusion competence in sperm. Any naturally occurring membrane fusion has two (...) major sequential steps: a docking or adhesion step, in which two membranes adhere, and a fusion step, in which their lipid bilayers are destabilized and merged and a cellular compartment is either created or destroyed. Recent evidence suggests that there is an important role for oocyte integrins and sperm‐bound disintegrins in mammalian sperm/oocyte adhesion and fusion. The fusion mechanism employed by sperm remains poorly understood, however, and circumstantial evidence suggests it is more complex than the interaction between a single protein species and its target. Sperm/oocyte fusion is probably the most accessible eukaryotic model for intercellular fusion currently available, partly because it is temporally separated from gene expression. Elucidation of the mechanism of sperm/oocyte fusion may throw light on the mechanism of other intercellular fusions such as myoblast fusion, and the evolutionary relationship of intercellular membrane fusion to intracellular membrane fusion. (shrink)

Protein misfolding is a topic that is of primary interest both in biology and medicine because of its impact on fundamental processes and disease. In this review, we revisit the concept of protein misfolding and discuss how the field has evolved from the study of globular folded proteins to focusing mainly on intrinsically unstructured and often disordered regions. We argue that this shift of paradigm reflects the more recent realisation that misfolding may not only be an adverse event, as originally (...) considered, but also may fulfil a basic biological need to compartmentalise the cell with transient reversible granules. We nevertheless provide examples in which structure is an important component of a much more complex aggregation behaviour that involves both structured and unstructured regions of a protein. We thus suggest that a more comprehensive evaluation of the mechanisms that lead to aggregation might be necessary. (shrink)

It is suggested that bifurcation of parallel fibres in the cerebellar cortex assists the spatiotemporal convergence of temporally dispersed and asomatotopic inputs to granule cells. This increases the number of combinations of inputs which can be compared for the purpose of sequence recognition.

In the mouse, at least 16 genes regulate vesicle trafficking to specialized lysosome‐related organelles, including platelet dense granules and melanosomes. Fourteen of these genes have been identified by positional cloning. All 16 mouse mutants are models for the genetically heterogeneous human disease, Hermansky–Pudlak Syndrome (HPS). Five HPS genes encode known vesicle trafficking proteins. Nine genes are novel, are found only in higher eukaryotes and encode members of three protein complexes termed BLOCs (Biogenesis of Lysosome‐related Organelles Complexes). Mutations in murine (...) HPS genes, which encode protein co‐members of BLOCs, produce essentially identical phenotypes. In addition to their well‐known effects on pigmentation, platelet function and lysosome secretion, HPS genes control a wide range of physiological processes including immune recognition, neuronal functions and lung surfactant trafficking. Studies of the molecular functions of HPS proteins will reveal important details of vesicle trafficking and may lead to therapies for HPS. BioEssays 26:616–628, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

Paraspeckles are nuclear condensates, or membranelees organelles, that are built on the long noncoding RNA, NEAT1, and have been linked to many diseases. Although originally described as constitutive structures, here, in reviewing this field, we develop the hypothesis that cells increase paraspeckle abundance as part of a general stress response, to aid pro‐survival pathways. Paraspeckles increase in many scenarios: when cells transform from one state to another, become infected with viruses and bacteria, begin to degenerate, under inflammation, in aging, and (...) in cancer. Cells increase paraspeckles by increasing transcription of NEAT1 and adjusting its RNA processing. These increases in NEAT1 are driven by numerous stress‐sensing signaling pathways, including signaling to mitochondria and stress granules, revealing crosstalk between the cytoplasm and nucleoplasm in the stress response. Thus, paraspeckles are an important piece of the puzzle in cellular homeostasis, and could be considered RNA‐scaffolded nuclear equivalents of dynamic stress‐induced structures that form in the cytoplasm. We speculate that, in general, cells rely on phase‐separated paraspeckles to transiently tweak gene regulation in times of cellular flux. (shrink)

Mormyrid teleosts have Purkinje cells with palisade dendrites, which probably represent coincidence detectors of parallel fiber activity. Their existence strongly supports the ideas of Braitenberg et al. on cerebellar function. However, the organization of mormyrid granule cells and parallel fibers suggests that a key to cerebellar function is not in interactions within one wave, but between twoopposite tidal waves.

Oogenesis being performed in the ovary shows two different kinds of nuclei in the nursing cells. The above mentioned nuclei are transferred and incorporated into the nuclei of developing eggs, which become sexually differentiated and showWolanski's methyl-green reaction. The sex determination is, therefore, cytologically progamic and genotypical. The spawned eggs in the jelly strings appear first of identical shape and are all coated from the very beginning with grainy bonellian pigment, but afterwards, being reared in free water cultures in the (...) absence of females, they differentiate into distinctly different male and female larvae. The numerical ratio of the sexually differentiated larvae is discussed. The true chromosomes in gamogenesis as well as in somatic cells have not been found. L'oogénèse qui a lieu dans l'ovaire montre deux sortes de noyaux dans les cellules nourricières. Les noyaux mentionnés ci-dessus sont transportés dans les noyaux des ovules en voie de développement qui se différencient sexuellement et montrent la réaction deWolanski au vert de méthyle. Le déterminisme du sexe est, par conséquent progamique et génotypique, du point de vue cytologique. Les ovules déposés en gelée sont d'abord de forme identique et sont tous recouverts, dès le début, du pigment granulé de boneliéne, mais, élevés par la suite, dans des cultures en eau courante, en l'absence des femelles, ils se différencient distinctement en larves mâles et femelles. La proportion numérique des larves différenciées sexuellement est discutée. Dans la gamétogénèse, comme dans les cellules somatiques, les vrais chromosomes restent introuvables. Während der Oogenese, die sich im Eierstock abspielt, zeigen sich zwei differente Kerntypen in den Nährzellen. Diese Kerne werden allmählich in die Kerne des sich entwickelnden Eies übertragen und dort inkorporiert. Das Ei wird dadurch geschlechtlich differenziert und zeigt dann dieWolanski's Methyl-grün Reaktion. Die sexuelle Determination ist somit progam und genotypic. Die in schnurartigen Gallerten abgelegten Eier sind am Beginn von gleicher Form und Grösse, so wie von Anfang an mit Körnchen des Pigmentes Bonellein bekleidet. In freien Wasserkulturen,ohne Weibchen, entwickeln sie sich in deutlich differenzierte männliche und weibliche Larven. Das numerische Verhältniss der geschlechtlich differenten Larven wird diskutiert. Echte Chromosomen sind weder bei der Gamogenese noch in somatischen Zellen gefunden worden. (shrink)

Platelets have important hemostatic functions in repairing blood vessels upon tissue injury. Cytokines, growth factors, and metabolites stored in platelet α‐granules and dense granules are released upon platelet activation and clotting. Emerging evidence indicates that such platelet‐derived signaling factors are instrumental in guiding tissue regeneration. Here, we discuss the important roles of platelet‐secreted signaling factors in skeletal muscle regeneration. Chemokines secreted by platelets in the early phase after injury are needed to recruit neutrophils to injured muscles, and impeding (...) this early step of muscle regeneration exacerbates inflammation at later stages, compromises neo‐angiogenesis and the growth of newly formed myofibers, and reduces post‐injury muscle force production. Platelets also contribute to the recruitment of pro‐regenerative stromal cells from the adipose tissue, and the platelet releasate may also regulate the metabolism and proliferation of muscle satellite cells, which sustain myogenesis. Therefore, harnessing the signaling functions of platelets and the platelet secretome may provide new avenues for promoting skeletal muscle regeneration in health and disease. (shrink)

In this article I present some characteristics of logics and semantics of an uncertain world. I confront two-valued and fuzzy logic. I use Kafka’s novel Process as an example, which is designed as an uncertain context with words which are rigid designators without rigid meaning. That produces an uncertain world of logical and semantical relations. In presentation of problems I introduce basic concepts of Frege’s, Wittgenstein’s, Tarsky’s, Searle’s, Quine’s and Davidson’s philosophy of language. I differ the logical and semantical identification (...) of identity. I differ reference and inference, or representation and identification as two components which are fundamental for the identification of identity. I found this difference on the role of logical unification and granulation of predicates in the structure of thought and semantical unification and granulation of attributes in the structure of statements and their relation to ontology of context. Through the confrontation of the logical and semantical unification and granulation I find that the limits of logic are not also the limits of language. The semantical unification goes over the highest genre and below the lowest species. That enables the extra-logical, non-scientifical, con-fessional, pro-phetical, artistic, and ordinary use of language. (shrink)

In this article I present some characteristics of logics and semantics of an uncertain world. I confront two-valued and fuzzy logic. I use Kafka’s novel Process as an example, which is designed as an uncertain context with words which are rigid designators without rigid meaning. That produces an uncertain world of logical and semantical relations. In presentation of problems I introduce basic concepts of Frege’s, Wittgenstein’s, Tarsky’s, Searle’s, Quine’s and Davidson’s philosophy of language. I differ the logical and semantical identification (...) of identity. I differ reference and inference, or representation and identification as two components which are fundamental for the identification of identity. I found this difference on the role of logical unification and granulation of predicates in the structure of thought and semantical unification and granulation of attributes in the structure of statements and their relation to ontology of context. Through the confrontation of the logical and semantical unification and granulation I find that the limits of logic are not also the limits of language. The semantical unification goes over the highest genre and below the lowest species. That enables the extra-logical, non-scientifical, con-fessional, pro-phetical, artistic, and ordinary use of language. (shrink)

In 2003, Nick Bostrom published his highly influential “Simulation Argument” in _Philosophical Quarterly_(Bostrom, 2003), an idea taken so seriously that even Bank of America has sent out alerts to its clients. But what, exactly, would that mean? And, more importantly, why is the idea of a simulated universe not being pursued in regard to cancer—and every other disease? We understand, in magnificently precise, granular ways, exactly what is going wrong in the body. But do we understand, in a coarser way, (...) what the granules are made of? In a holographic universe, the images we perceive are not necessarily what they appear to be; they might exist against a background. But the background would create a context that participates in the image that emerges. Green can be rendered as green. Or as “blue yellow blue” or “yellow blue yellow.” Perhaps the act of rendering generates variables that have been overlooked in our understanding of illness: scale and spin. (shrink)