Fully grown Xenopus oocytes can remain in their immature state essentially indefinitely, or, in response to the steroid hormone progesterone, can be induced to develop into fertilizable eggs. This process is termed oocyte maturation. Oocyte maturation is initiated by a novel plasma membrane steroid hormone receptor. Progesterone brings about inhibition of adenylate cyclase and activation of the Mos/MEK1/p42 MAP kinase cascade, which ultimately brings about the activation of the universal M phase trigger Cdc2/cyclin B. Oocyte (...) maturation provides an interesting example of how signaling cascades entrain the cell cycle clock to environmental changes. BioEssays 21:833–842, 1999. © 1999 John Wiley & Sons, Inc. (shrink)

The oocyte is not only the rarest and the largest cell in the body, but it also has one of the most remarkable life histories. Formed in the fetal ovary and suspended at diplotene of meiosis, it may wait for years before beginning to grow, and not until this process is complete can it resume meiosis and undergo fertilisation. Major changes in the number, morphology and distribution of cytoplasmic organelles occur during growth, and a molecular program for embryogenesis is (...) formed. Specific yolk proteins are absent and much of the RNA and some of the protein are degraded by the cleavage stage. The zona pellucida has been intensively studied, but knowledge of oocyte‐specific genes is otherwise surprisingly patchy given the significance of this cell type and the expansion of reproductive technology. Finally, it is now clear that oocytes are not mere passengers which depend on granulosa cells for nutrition and regulation but actively promote the growth and differentiation of their follicles. (shrink)

What makes something an embryo—as opposed to what is actually, and not just in biotech parlance, a collection of cells? This question has come to the fore in recent years with proposals for producing embryonic stem cells for research. While some of those opposed to use of standard embryonic stem cells emphasise that adult cells have a clinical track record, others argue that there may be further benefits obtainable from cells very like those of embryos, provided such cells can be (...) derived in new ways. Rather than deriving them in ways that kill or otherwise endanger a living human embryo, they could be obtained from an entity that merely resembles a human embryo sufficiently closely for its cells to be of use. Such an entity might be created after introducing genetic changes to an ovum before it is activated by, for example, a cloning-type procedure, such that a gene essential to embryogenesis will be either absent, blocked in its expression, or overexpressed.1,2 The claim is that the ovum could be made to give rise to embryonic stem cells—mere living parts—without ever giving rise to a whole embryo, who is killed to obtain them. Whereas cloning “proper” winds back the specialisation of the cell nucleus to a point where a whole embryo is formed who has not yet specialised its cells, oocyte-assisted reprogramming , it is claimed, would wind back the specialisation merely to an intermediate point at which no embryo is created. Other methods proposed for deriving pseudoembryonic cells include parthenogenesis, in which an ovum is activated without a sperm, or even the insertion of an adult cell nucleus.1MORAL STATUS OF THE EMBRYOIn this paper, I assume that a genuine …. (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)

Mammalian oocytes exhibit a series of cell cycle transitions that coordinate the penultimate events of meiosis with the onset of embryogenesis at fertilization. The execution of these cell cycle transitions, at G2/M of meiosis‐I and metaphase/anaphase of meiosis I and II, involve both biosynthetic and post‐translational modifications that directly modulate centrosome and microtubule behavior. Specifically, somatic cells alter the signal transduction pathways in the oocyte and influence the expression of maturation promoting factor (MPF) and cytostatic factor (CSF) activity through (...) a microtubule‐dependent mechanism. The regulation of the oocytes' cell cycle machinery by hormone‐mediated somatic cell signals, involving both positive and negative stimuli, ensures that meiotic cell cycle progression is synchronized with the earliest pivotal events of mammalian reproduction. (shrink)

One distinguishing feature of vertebrate oocyte meiosis is its discontinuity; oocytes are released from their prophase I arrest, usually by hormonal stimulation, only to again halt at metaphase II, where they await fertilization. The product of the c‐mos proto‐oncogene, Mos, is a key regulator of this maturation process. Mos is a serine‐threonine kinase that activates and/or stabilizes maturation‐promoting factor (MPF), the master cell cycle switch, through a pathway that involves the mitogen‐activated protein kinase (MAPK) cascade. Oocytes arrested at prophase (...) I lack detectable levels of Mos, which must be synthesized from a pool of maternal mRNAs for proper maturation. While Mos is necessary throughout maturation in Xenopus, it seems to be required only for meiosis II in the mouse. The translational activation of c‐mos mRNA at specific times during meiosis requires cytoplasmic polyadenylation. Cis‐ and trans‐acting factors for polyadenylation are, therefore, essential elements of maturation. (shrink)

Mos, a protein kinase, is specifically expressed and functions during meiotic maturation (or G2/M progression) of vertebrate oocytes. When expressed ectopically, however, it can also readily induce oncogenic transformation (or uncontrolled G1/S transitions) in somatic cells. In both of these cell types, Mos activates mitogen‐activated protein kinase (MAPK), which seems largely to mediate its different functions in both oocyte maturation and cellular transformation. In oocyte maturation, the Mos‐MAPK pathway probably serves to activate and stabilize M‐phase promoting factor (MPF) (...) (possibly by inhibiting some negative regulator(s) of this factor), while in cellular transformation, it seems to stabilize and activate the nuclear oncoprotein c‐Fos as well as to induce transcription of its gene. Thus, the different functions of Mos in oocytes and somatic cells may arise chiefly from its different MAPK‐mediated targets in the respective cell types. This review discusses the cellular basis that may enable Mos to act differently in oocytes and somatic cells. (shrink)

We have discovered that a single sperm protein, phospholipase C‐zeta (PLCζ), can stimulate intracellular Ca2+ signalling in the unfertilized oocyte (‘egg’) culminating in the initiation of embryonic development. Upon fertilization by a spermatozoon, the earliest observed signalling event in the dormant egg is a large, transient increase in free Ca2+ concentration. The fertilized egg responds to the intracellular Ca2+ rise by completing meiosis. In mammalian eggs, the Ca2+ signal is delivered as a train of long‐lasting cytoplasmic Ca2+ oscillations that (...) begin soon after gamete fusion and persist beyond the completion of meiosis. Sperm PLCζ effects Ca2+ release from egg intracellular stores by hydrolyzing the membrane lipid PIP2 and consequent stimulation of the inositol 1,4,5‐trisphosphate (InsP3) receptor Ca2+‐signalling pathway, leading to egg activation and early embryogenesis. Recent advances have refined our understanding of how PLCζ induces Ca2+ oscillations in the egg and also suggest its potential dysfunction as a cause of male infertility. (shrink)

This article develops a model of informed consent for fresh oöcyte donation for stem cell research, during in vitro fertilisation (IVF), by building on the importance of patients’ embodied experience. Informed consent typically focuses on the disclosure of material information. Yet this approach does not incorporate the embodied knowledge that patients acquire through lived experience. Drawing on interview data from 35 patients and health professionals in an IVF clinic in Australia, our study demonstrates the uncertainty of IVF treatment, and the (...) tendency for patients to overestimate their chances of success prior to the experience of treatment. Once in active treatment, however, patients identify their oöcytes as both precious and precarious. We argue that it is necessary to formally include embodied experience as a source of knowledge in informed consent procedures, both for gratuitous donation and for egg-sharing regimes. We recommend that at least one full cycle of IVF be completed before approaching women to divert eggs away from their own fertility treatment. (shrink)

The developing vertebrate oocyte autonomously makes most of the components of the machinery for DNA and protein synthesis, as well as ‘maternal’ mRNAs, needed immediately after fertilization. However, specialized egg constituents such as yolk proteins, egg white, cholesterol, lipoproteins and egg coat substances, are formed in the liver, oviduct and perhaps in follicle cells. The assembly of the developing egg is therefore a fascinating example of division of labor among oocytes and extra‐oocyte tissues, the coordination of activities of (...) the latter being achieved by hormones. (shrink)

The identification and valorization of unacknowledged, feminized forms of economic productivity has been an important task for feminist theory. In this article, we expand and rethink existing definitions of labour, in order to recognize the essential economic role women play in the stem cell and regenerative medicine industries, new fields of biomedical research that are rapidly expanding throughout the world. Women constitute the primary tissue donors in the new stem cell industries, which require high volumes of human embryos, oöcytes, foetal (...) tissue and umbilical cord blood. Such material is generally given for free in the advanced industrial democracies, constituted as a surplus (‘spare’ embryos) or waste (umbilical cord ‘afterbirth’, cadaveric foetuses, poor quality oöcytes) whose generative powers should not be withheld from others. At the same time, among impoverished female populations in developing nations, such biological material is now often procured through frankly transactional relations, where women undertake risky procedures for small fees. In each case, female bodily productivity is mobilized to support bioeconomic research, yet the economic value involved in these relations is largely unacknowledged. In this article, we consider both the gift economy and the transactional economy for reproductive tissues as a form of labour. In order to fully conceptualize the specificities of feminized productivity in the bioeconomy, we distinguish between earlier feminist theories of reproductive labour and the emerging practices generated by stem cell research, which we term regenerative labour. We consider how historical transformations in the regulation of feminized labour and the technical repertoires of stem cell research renegotiate the productivity limits of female reproductive biology, opening it out to novel and profitable forms of surplus value and enrolling women in complex negotiations over their role in bioeconomic activity. (shrink)

Chromosomes are not only carriers of the genetic material, but also actively regulate the assembly of complex intracellular architectures. During mitosis, chromosome‐induced microtubule polymerisation ensures spindle assembly in cells without centrosomes and plays a supportive role in centrosome‐containing cells. Chromosomal signals also mediate post‐mitotic nuclear envelope (NE) re‐formation. Recent studies using novel approaches to manipulate histones in oocytes, where functions can be analysed in the absence of transcription, have established that nucleosomes, but not DNA alone, mediate the chromosomal regulation of (...) spindle assembly and NE formation. Both processes require the generation of RanGTP by RCC1 recruited to nucleosomes but nucleosomes also acquire cell cycle stage specific regulators, Aurora B in mitosis and ELYS, the initiator of nuclear pore complex assembly, at mitotic exit. Here, we review the mechanisms by which nucleosomes control assembly and functions of the spindle and the NE, and discuss their implications for genome maintenance. (shrink)

Specification of the anterior‐posterior axis of the Drosophila embryo is brought about by the asymmetric localization of specific maternally expressed RNAs and proteins within the oocyte. While many of these localized molecules have been identified and progress has been made towards understanding their functions, how the localization process is instigated remains unclear. A recent paper reports that protein kinase A (PKA) activity is essential for many of these RNA localizations and for the correct polarization of the microtubule cytoskeleton(1). These (...) and other results support a model for anterior‐posterior axis establishment which involves intercellular signalling between the oocyte and certain neighbouring somatic cells. (shrink)

The risks associated with the techniques of medically assisted procreation (MAP) rapidly became well-known, and in such a short space of time that no biomedical domain remained untouched by the great deal of thinking and the expression of a multitude of opinions it provoked. MAP is evolving between two poles: quality/misuse (even violation) and evidence/fantasy. The ethics will be evoked in the clinical reality from which they spring and where their justification lies. The three objects common to these ethics, the (...) oocyte, the embryo and the child, are illustrated in this context. MAP has as its corollary access to the oocyte, the fertilization of which will take place in vitro. Access to the embryo, on the other hand, enables the clinician, for the purposes of diagnosis [preimplantation genetic diagnosis (PGD), predictive medicine], or even soon for therapeutic purposes (gene therapy) to draw close to a boundary, to trespass beyond which may be seen by humanity to threaten its very origins and integrity: the alienation of the human genome. For the infertile couple, the missing child may take on a dimension of which they would have been unaware, had they not been forced to express their desire. The burden of the imaginary child may, in this way, become a heavier load to bear when, after such desire, he comes into being. MAP puts the goal of normalisation within reach and, in doing so, accentuates the risk of the burden of the attributed representation of the child. On the one hand, MAP offers a tremendous diagnostic and therapeutic potential, while on the other it opens the door to excess and delirium. In this melting pot, ethics, catalysed by this new source of problematics, has discovered a favourite area in which to define and redefine itself. We propose the intervention of ethics on three different levels. Before the elaboration of the law: on first reflection, ethics may influence the responsibilities of the legislator, by taking care that the law does not obscure the biomedical and socioeconomic contexts of MAP and, thereby, also include other related and complementary aspects dealing with the same subject. The secondary discussion of ethics should influence the application of legal protection, by taking into account the rapid technological and social development of MAP, there too, by discussing the whole, rather than the details which will obscure the object. The ethical reflection of the clinician, who is aware of these difficulties, is guided by elements that are specific to his position as a doctor. The cohesion of the team around the clinician and the ethics specialist enables us to develop consensual clinical ethics that are transmissible and therefore teachable. This complex role can, in our view, only be acted out directly in the clinical situation, where the constant, direct relationship with the object of the reflection and the treatment allows ethics to take into account the contingencies of medical practice: we invite the ethics specialist to take part in our clinical activity on a daily basis. (shrink)

The ovarian tumor (otu) gene behaves as if it encodes a product (OGP) which is required during several early steps in the transformation of oogonia into functional oocytes. The ovarian phenotypes produced by various EMS‐induced mutations can be explained as graded responses by individual mutant germ cells to the different levels of functionally active OGP they themselves synthesize. In addition, genetic evidence suggests that otu also encodes a second product that is utilized late in oogenesis. Molecular studies of the otugene (...) demonstrate that it does transcribe at least two ovaryspecific RNAs. The possible function of the otu product in the cellular divisions that give rise to the oocyte and its sister nurse cells is discussed. (shrink)

Sex determination in most organisms involves a simple binary fate choice between male or female development; the outcome of this decision has profound effects on organismal biology, biochemistry and behaviour. In the nematode C. elegans, there is also a binary choice, either male or hermaphrodite. In C. elegans, distinct genetic pathways control somatic and germline sexual cell fate. Both pathways share a common set of globally acting regulatory genes; however, germline-specific regulatory genes also participate in the decision to make male (...) or female gametes. The determination of sexual fate in the germline of the facultative hermaphrodite poses a special problem, because first sperm then oocytes are produced. It has emerged that additional layers of post-transcriptional regulation have been imposed to modulate the activities of the global sex-determining genes, tra-2 and fem-3; the balance between these activities is crucial in controlling sexual cell fate in the hermaphrodite germline. BioEssays 23:596–604, 2001. © 2001 John Wiley & Sons, Inc. (shrink)

Transcription and replication of genes in mammalian cells always requires a promoter or replication origin, respectively, but the ability of enhancers to stimulate these regulatory elements and the interactions that mediate this stimulation are developmentally acquired. The primary function of enhancers is to prevent repression, which appears to result from particular components of chromatin structure. Factors responsible for this repression are present in the maternal nucleus of oocytes and its descendant, the maternal pronucleus of mouse 1‐cell embryos and in mouse (...) 2‐cell embryos, but are absent in the paternal pronucleus. Thus, enhancers are not needed to achieve efficient transcription and replication in paternal pronuclei. However, enhancers, even in the presence of their specific activation protein, are inactive prior to formation of a 2‐cell embryo, suggesting that a coactivator essential for enhancer function is not available until zygotic gene expression begins. Furthermore, enhancer stimulation of transcription appears to be mediated through a promoter transcription factor, but this interaction can change as cells undergo differentiation, switching from a TATA‐box independent to a TATA‐box dependent mode. (shrink)

Going back to the late 1970s and early 1980s, we trace the Xenopus oocyte microinjection experiments that led to the emergence of the concept of “modulator”. The finding that the modulator could transactivate transcription from far upstream and in either orientation suggested that a new genetic element, different from the classical prokaryotic promoter sequences, had been discovered. This particular enhancer transactivates transcription of the sea urchin early (α) histone H2A gene which is regulated in early sea urchin development. We (...) summarise the data from sea urchin microinjection experiments that confirm and extend the results obtained with Xenopus oocytes. We conclude that the H2A enhancer is bipartite, is located approx. 100 bp upstream of the TATAAATA box in the H2A gene of two sea urchin species and enhances transcription when placed at a position far upstream or far downstream of the gene unless an insulator intervenes between enhancer and promoter. Evidence from microinjection experiments with sea urchin embryos suggests that the developmental control of H2A expression resides not with the enhancer, which is constitutively active, but with a striking chromatin structure with two positioned nucleosomes near the 3′ end of the gene. Within this structure, there is an insulator element. BioEssays 24:850–857, 2002. © 2002 Wiley Periodicals, Inc. (shrink)

The poly(A)‐dependent translational regulation of maternal mRNAs is an important mechanism to execute stage‐specific programs of protein synthesis during early development. This control underlies many crucial developmental events including the meiotic maturation of oocytes and activation of the mitotic cell cycle at fertilization. A recent report(1) demonstrates that the 3′ untranslated region of the cyclin A1, B1, B2 and c‐mos mRNAs determines the timing and extent of their cytoplasmic polyadenylation and translational activation during Xenopus oocyte maturation. These (...) studies further establish that protein synthesis can be temporally and quantitatively controlled by developmentally regulated changes in the polyadenylation of maternal mRNAs. (shrink)

Although the generation of reactive oxygen species is an activity normally associated with phagocytic leucocytes, mammalian spermatozoa were, in fact, the first cell type in which this activity was described. In recent years it has become apparent that spermatozoa are not the only nonphagocytic cells to exhibit a capacity for reactive oxygen species production, because this activity has been detected in a wide variety of different cells including fibroblasts, mesangial cells, oocytes, Leyding cells endothelial cells, thryroid cells, adipocytes, tumour cell (...) and platelets. Since the capacity to generate reactive oxygen species is apparently so widespread, the risk‐benefit equation for these potentially pernicious molecules becomes a matter of intese interest. In the case of human spermatozoa, the risk of manufacturing reactive oxygen metabolites is considerable because these cells are particularly vulnerable to lipid peroxidation. Indeed, there is now good evidence to indicate that oxygen radicals are involved in the initiation of peroxidative damage to the sperm plasma membrane, seen in many cases of male infertility. This risk is off‐set by recent data suggesting that superoxide anions and hydrogen peroxide also participate in the induction of key biological events such as hyperactiavated motility and the acrosome reaction. Thus, human spermatozoa appear to use reactive oxygen species for a physiological purpose and have the difficult task of ensuring the balanced generation of these potentially harmful, but biologically important, modulators of cellular function. (shrink)

In the face of rapid technological developments and growing economic pressures, governments around the world are being called upon to regulate activities in the realm of biotechnology. My aim in this paper is to argue that core conceptual insights of feminist ethics are essential to ethically adequate policy-making in this area. Specifically, I shall argue that development of ethical biotechnology require that policy-makers undergo an ontological shift from the currently widespread assumptions of the dominant political framework of liberal individualism to (...) an explicitly feminist understanding of subjects as relational beings. To ground my discussion, I shall explore the field of reproductive technologies, especially as they are used for genetic “improvements.” I shall pay particular attention to the use ofin vitrofertilization in conjunction with pre-implantation genetic diagnosis and related variations.Briefly, IVF, the core technology of so-called new reproductive technologies, is a platform technology that facilitates many other practices through affording access to oocytes and embryos. (shrink)

Multidisciplinary studies have led to the discovery and characterization of cysteine string proteins (csps) in both Drosophila and Torpedo. Phenotypic analysis of csp mutants in Drosophila demonstrates a crucial role for csp in synaptic transmission. Expression studies of Torpedo csp (Tcsp) in Xenopus oocytes suggests that the protein has some role in the function of presynaptic Ca2+ channels. However, biochemical purification of Tcsp indicates that is associated with synaptic vesicles rather than with the plasma membrane of presynaptic terminals where Ca2+ (...) channels reside. These results suggest a model in which csps serve as a link by which docked synaptic vesicles could modulate the activity of presynaptic Ca2+ channels. (shrink)

In many animal species, the early development of the embryo follows a stereotypic pattern of cell cleavage, lineage allocation and generation of tissue asymmetry leading to delineation of the body plan with three primary embryonic axes. The mammalian embryo has been regarded as an exception and primary body axes of the mouse embryo were thought to develop after implantation. However, recent findings have challenged this view. Asymmetry in the fertilised oocyte, as defined by the position of the second polar (...) body and the sperm entry point, can be correlated with the orientation of the animal–vegetal and the embryonic–abembryonic axes in the preimplantation blastocyst. Studies of the pattern of morphogenetic movement of cells and genetic activity in the peri‐implantation embryo suggest that the animal–vegetal axis of the blastocyst might presage the orientation of the anterior–posterior axis of the gastrula. This suggests that the asymmetry of the zygote that is established at fertilisation and early cleavage has a lasting impact on the delineation of body axes during embryogenesis. BioEssays 23:508–517, 2001. © 2001 John Wiley & Sons, Inc. (shrink)

The bulk of the DNA in eukaryotic chromatin behaves as if it is topologically relaxed; however, a subfraction can be shown to be under suercoil tension. Endonuclease S1 cuts at specific hypersentive sites in chromatin (in the promoter regions of active genes) and this enzyme cuts in the same region in supercoiled plasmids, but not in relaxed or linearized molecules. A subfraction of the minichromosomes formed after SV40 infection or microinjection of plasmid DNA into oocytes contains supercoil tension and this (...) subfraction is thought to play an important role in transcription. (shrink)

The chromosomes undergo a condensation‐decondensation cycle within the life cycle of mammalian cells. Chromosome condensation is a complex and critical event that is necessary for the equal distribution of genetic material between the two daughter cells. Although chromosome condensation‐decondensation and segregation is mechanistically complex, it proceeds with high fidelity during the eukaryotic cell division cycle. Cell fusion studies have indicated the presence of chromosome condensation factors in mammalian cells during mitosis. If extracts from mitotic cells are injected into immature oocytes (...) of Xenopus laevis, they induce meiotic maturation (i.e. germinal vesicle breakdown and chromosome condensation) within 2–3 hours. Recently, we showed that the maturation‐promoting activity of the mitotic cell extracts is inactivated by certain protein factors present in cells during the G1 period. The activity of the G1 factors coincides with the process of chromosome decondensation that begins at telophase and continues throughout the G1 period. These studies have revealed that the mitotic factors and the G1 factors play a pivotal role in the regulation of condensation and decondensation of chromosomes. Furthermore, our studies strongly suggest that nonhistone protein phosphorylation and dephosphorylation may mediate chromosome condensation and decondensation, respectively. (shrink)

Feedback loops have been identified in a variety of regulatory systems and organisms. While feedback loops of the same type (negative or positive) tend to have properties in common, they can play distinctively diverse roles in different regulatory systems, where they can affect virulence in a pathogenic bacterium, maturation patterns of vertebrate oocytes and transitions through cell cycle phases in eukaryotic cells. This review focuses on the properties and functions of positive feedback in biological systems, including bistability, hysteresis and (...) class='Hi'>activation surges. BioEssays 30:542–555, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

The principles of automation in animal development, as previously inferred from the concept of Cell Sociology do not fit in well with the current concept of sequential gene derepression. A more adequate explanation for those principles has been found in the literature dealing with the biochemical aspects of differentiation. Since oocytes and embryonic cells contain a greater variety of mRNAs than differentiated cells, as well as many tissue-specific (luxury) substances, it is concluded that the diversification of tissues consists of a (...) progressive selection of specific metabolic strategies, mediated by cell-to-cell contacts, from a broad range of pre-existing strategies. For each tissue, prior to its final determination, one luxury metabolic strategy is progressively intensified and becomes dominant. The others are either suppressed or maintained as latent metabolic strategies. The latter may on occasion become dominant again (transdifferentiation). These phenomena require a theory which considers gene regulation as the activation of otherwise repressed genes by specific activator RNAs. The high (apparently maximal) transcriptional activity on the lampbrush chromosomes may represent the synthesis of all the kinds of activator RNAs which are required for the reactivation of the genes during early development. A general conception is propounded of the automatism and programming of animal development, as inferred from the confrontation of these ideas with the concept of Cell Sociology. (shrink)

ART and, in particular, IVF and ICSI, are essentially a laboratory experiment, but which, due to its specificity, goes beyond the disciplinary boundaries, explicitly acquiring an ethical-axiological dimension in the interaction zone of the members of a particular community involved in child-bearing. At the same time, it is noted that the activity and choice of a way to solve problems with childbirth has a characteristic severity, due to the traditions and level of civil and social maturity of a country, due, (...) among other things, to the level and achievements of technical equipment in this industry of knowledge and practice. According to foreign studies, about half of all subfertile people in developed countries are trying to overcome their infertility with the help of medicine, and research data indicate that the proportion of such individuals is growing. The most difficult problems of reproduction are associated with low quality of oocytes or low ovarian reserve ; aspermia and deep teratozoospermia, can not give hope to a couple to have genetically related offspring. However, donor programs create additional opportunities for social motherhood / paternity. Donation of oocytes is found in ART programs at least 3 times more often than donation of spermatozoa. At the moment, donation of gametes and embryos raises a number of ethical, legal, medical and socio-psychological issues that require competent support from experts of a wide range of specialists, as well as competent, non-commercial, primarily due to the interaction between donors and recipients. The analysis of possible modifications of family and kinship ties is based on the idea of transforming social relations, in which assisted reproductive technologies play a fundamental role, building a system of “new kinship and new family.” By entering into the intimate process of the birth of life and acting as a regulator of the composition of participants in this process through the stimulation of responsibility to present and future relatives, reproductive technologies affect the initial moral requirements in the community, redefining universal values based on the specific situation. Scenarios of childbearing through ART with the involvement of additional participants are possible in the context of the legal field, but legally fixed anonymity of the donor leaves many unresolved issues related to the problems of hereditary diseases, genetic abnormalities and epigenetic changes; in addition, there is a problem associated with the possibility of unintentional incest, as well as the difficulties of the child’s self-identification and the closeness of his genealogy. Solutions to these issues are postponed until later, thereby initiating future dramatic situations, ethical conflicts and dilemmas with a poorly predictable positive outcome. (shrink)

Goal‐directed cognition is often discussed in terms of specialized memory structures like the “goal stack.” The goal‐activation model presented here analyzes goal‐directed cognition in terms of the general memory constructs of activation and associative priming. The model embodies three predictive constraints: (1) the interference level, which arises from residual memory for old goals; (1) the strengthening constraint, which makes predictions about time to encode a new goal; and (3) the priming constraint, which makes predictions about the role of (...) cues in retrieving pending goals. These constraints are formulated algebraically and tested through simulation of latency and error data from the Tower of Hanoi, a means‐ends puzzle that depends heavily on suspension and resumption of goals. Implications of the model for understanding intention superiority, postcompletion error, and effects of task interruption are discussed. (shrink)

Background Speech understanding may rely not only on auditory, but also on visual information. Non-invasive functional neuroimaging techniques can expose the neural processes underlying the integration of multisensory processes required for speech understanding in humans. Nevertheless, noise (from fMRI) limits the usefulness in auditory experiments, and electromagnetic artefacts caused by electronic implants worn by subjects can severely distort the scans (EEG, fMRI). Therefore, we assessed audio-visual activation of temporal cortex with a silent, optical neuroimaging technique: functional near-infrared spectroscopy (fNIRS). (...) Methods We studied temporal cortical activation as represented by concentration changes of oxy- and deoxy-hemoglobin in four, easy-to-apply fNIRS optical channels of 33 normal-hearing adult subjects and 5 post-lingually deaf cochlear implant (CI) users in response to supra-threshold unisensory auditory and visual, as well as to congruent auditory-visual speech stimuli. Results Activation effects were not visible from single fNIRS channels. However, by discounting physiological noise through reference channel subtraction, auditory, visual and audiovisual speech stimuli evoked concentration changes for all sensory modalities in both cohorts (p<0.001). Auditory stimulation evoked larger concentration changes than visual stimuli (p<0.001). A saturation effect was observed for the audiovisual condition. Conclusions Physiological, systemic noise can be removed from fNIRS signals by reference channel subtraction. The observed multisensory enhancement of an auditory cortical channel can be plausibly described by a simple addition of the auditory and visual signals with saturation. (shrink)

Creating focal lesions in primary visual cortex (V1) provides an opportunity to study the role of extra-geniculo-striate pathways for activating extrastriate visual cortex. Previous studies have shown that more than 95% of neurons in macaque area V2 and V3 stop firing after reversibly cooling V1 [1,2,3]. However, no studies on long term recovery in areas V2, V3 following permanent V1 lesions have been reported in the macaque. Here we use macaque fMRI to study area V2, V3 activity patterns from 1 (...) to 22 months after lesioning area V1. We find that visually driven BOLD responses persist inside the V1-lesion projection zones (LPZ) of areas V2 and V3, but are reduced in strength by ,70%, on average, compared to prelesion levels. Monitoring the LPZ activity over time starting one month following the V1 lesion did not reveal systematic changes in BOLD signal amplitude. Surprisingly, the retinotopic organization inside the LPZ of areas V2, V3 remained similar to that of the non-lesioned hemisphere, suggesting that LPZ activation in V2, V3 is not the result of input arising from nearby (non-lesioned) V1 cortex. Electrophysiology recordings of multi-unit activity corroborated the BOLD observations: visually driven multi-unit responses could be elicited inside the V2 LPZ, even when the visual stimulus was entirely contained within the scotoma induced by the V1 lesion. Restricting the stimulus to the intact visual hemi-field produced no significant BOLD modulation inside the V2, V3 LPZs. We conclude that the observed activity patterns are largely mediated by parallel, V1-bypassing, subcortical pathways that can activate areas V2 and V3 in the absence of V1 input. Such pathways may contribute to the behavioral phenomenon of blindsight. (shrink)

BackgroundSubjective cognitive decline, non-amnestic mild cognitive impairment, and amnestic mild cognitive impairment are regarded to be at high risk of converting to Alzheimer’s disease. Amplitude of low-frequency fluctuations can reflect functional deterioration while diffusion tensor imaging is capable of detecting white matter integrity. Our study aimed to investigate the structural and functional alterations to further reveal convergence and divergence among SCD, naMCI, and aMCI and how these contribute to cognitive deterioration.MethodsWe analyzed ALFF under slow-4 and slow-5 bands and white matter (...) fiber integrity among normal controls, SCD, naMCI, and aMCI groups. Correlation analyses were further utilized among paired DTI alteration, ALFF deterioration, and cognitive decline.ResultsFor ALFF calculation, ascended ALFF values were detected in the lingual gyrus and superior frontal gyrus within SCD and naMCI patients, respectively. Descended ALFF values were presented mainly in the LING, SFG, middle frontal gyrus, and precuneus in aMCI patients compared to CN, SCD, and naMCI groups. For DTI analyses, white matter alterations were detected within the uncinate fasciculus in aMCI patients and within the superior longitudinal fasciculus in naMCI patients. SCD patients presented alterations in both fasciculi. Correlation analyses revealed that the majority of these structural and functional alterations were associated with complicated cognitive decline. Besides, UF alterations were correlated with ALFF deterioration in the SFG within aMCI patients.ConclusionsSCD shares structurally and functionally deteriorative characteristics with aMCI and naMCI, and tends to convert to either of them. Furthermore, abnormalities in white matter fibers may be the structural basis of abnormal brain activation in preclinical AD stages. Combined together, it suggests that structural and functional integration may characterize the preclinical AD progression. (shrink)

Binding of antigen or lectin to the surface of a T lymphocyte initiates a complex sequence of events which result in both T cell proliferation and the acquisition of immunologic functions. This complex sequence of events is most likely programmed and precisely timed by a series of contingent gene activations in which one member of this series activates the next. The two most obvious examples of these stages are the set of genes activated when antigen interacts with the antigen receptor (...) and the set of genes activated when IL‐2 interacts with its receptor. However, it is likely that several other parallel pathways of gene activation are necessary to bring about T‐cell division. An example would be the antigen‐induced activation of the c‐myc gene, which in turn is likely to be involved in regulating an additional group of genes not directly controlled by either IL‐2 or antigen. A fundamental understanding of T‐lymphocyte activation necessitates identification of the factors involved in initiating each of these contingent levels of gene activation. (shrink)

Both Solms and Nielsen acknowledge the difficulty of accounting for the similarities between REM and NREM sleep mentation with a two-generator model, and each link dreams, either explicitly (Solms) or implicitly (Nielsen), to brain activation. At present, however, no data indicate that brain activation can be demonstrated whenever vivid dream reports are obtained. [Nielsen; Solms].

This paper explores the consequences of the theoretical forward activation enzymatic pathway A 0 A 1 A 2 A 3 where E 1 convents A 0 to A 1, E 2 converts A 1 to A 2 and E 3 converts A 2 to A 3. A 0, which is environmentally determined, also serves to activate (or modulate) the activity of E 3 in such a way as to keep the concentration of A 2 ([A 2]) constant at a (...) particular set-point value. For mathematical simplicity, first order rate kinetics are used where k 1, k 2 and k 3 are the rate constants for E 1, E 2, and E 3 respectively. It is shown that if k 3 is modulated appropriately so as keep [A 2] at the setpoint value with a changing upstream [A 0], then the modulation of k 3 must be anticipatory of the dynamics of the biochemical pathway. In other words, the rate of change of k 3, will be a function of [A 0], k 1, k 2, k 3, and the set-point value of [A 2]. If the modulation of k 3 does not perfectly model (anticipate) the reaction pathway of which it is a part, then the actual [A 2] will deviate from the set-point value. This type of anticipatory feed-forward activation may represent an important aspect of biological organization. (shrink)