Metaphysics to the rescue?: Four-dimensionalism and the twinning argument against conceptionism

The view that human beings begin to exist at fertilization (namely conceptionism) faces a serious challenge from the twinning argument, that identical twins coming from the same zygote must be numerically distinct from the zygote and so did not exist at fertilization. Recently, some philosophers have claimed that the twinning argument rests on a particular metaphysical theory of persistence, namely endurantism, on which a human being, for example, is wholly present at every moment of her existence. And we can easily refute the argument, they claim, by employing perdurantism or exdurantism, according to which a human being is a temporally extended entity with temporal parts or a momentarily existing stage who has other momentarily existing stages as counterparts. I argue that such claims are mistaken. The twinning argument does not rest on endurantism and can be formulated in terms of perdurantism to provide a good reason for perdurantists to reject conceptionism. And exdurantism does not have any advantage in defending conceptionism either, for it already concedes more than what the twinning argument aims to show.     

A study of the occurrence of monochorionic and monozygotic twinning in the pig

In humans as well as in most farm animals, monozygotic twins have been described. Nevertheless, only a few reports of twinning in the pig have been published. It has been suggested that monozygotic twins are formed during the first 14 days of pregnancy. This monozygotic twin study includes the investigation of porcine monochorionic embryos from 76 sows at days 26–29 post-insemination (p.i.), as well as an examination of 10 whole litters at days 21–22 p.i. In the former group, 29% of the sows carried monochorionic embryos. Based on DNA profiling using microsatellite markers, one monozygotic twin pair was found among these embryos. In the latter group, three monozygotic twin pairs were identified. Thus, it can be concluded that although the occurrence of monozygotic twins in pigs is a sporadic event, the fusion of extra-embryonic membranes is relatively common.     

A deleterious effect associated with UNH159 is attenuated in twin embryos of an inbred line of blue tilapia Oreochromis aureus

Offspring of a highly inbred gynogenetic line of Oreochromis aureus displayed 12‐fold increase in twinning rate compared to the outbred population. Asymmetric conjoined twins, which consist of a normal embryo attached to a malformed‐atrophic twin, were frequently encountered in both gynogenetic (90·7%) and outbred (38·2%) embryos. The monozygotic origin of these twins was determined using five microsatellite markers. Progeny of heterozygous parents for the microsatellite UNH159 were separated into sub‐sets of twins and normal full‐sibs. Consistent with previous reports, the normal embryo sub‐set exhibited elimination of both types of homozygotes for the UNH159 genetic marker at 2–8 days after fertilization. Unexpectedly, this elimination was less frequent in twins. The UNH159 marker as well as RNA‐binding motif protein, X‐linked (rbmx), SRY‐box containing gene 3 (sox3) and alpha‐thalassemia/mental retardation syndrome X‐linked (atrx) genes were mapped to linkage group 2. These gene orthologues are all located on the mammalian X chromosome and atrx is necessary for the X‐chromosome inactivation.     

Isolation of protoplasts from zygotes of Fucus distichus (L.) powell (Phaeophyta)

Two-step procedures were developed for the isolation of protoplasts from 6-hour-old zygotes of Fucus distichus L., using commercial cellulases and alginate-lyases from marine molluscs. Protoplasts were obtained either as a suspension or attached to a substratum. Protoplasts yields were greater than 95% of the cell population and over 80% regenerated a wall, germinated and divided into a polar, multicellular embryo. Zygote development from regenerated protoplasts was also quite synchronous. The same procedures were less effective in removing the cell wall from zygotes older than 8 h, and did not yield significant numbers of protoplasts from two-celled embryos.     

A ZYGOTE COULD BE A HUMAN: A DEFENCE OF CONCEPTIONISM AGAINST FISSION ARGUMENTS

In this paper I defend the view that a zygote is a human from the fission objection that is widely thought to be decisive against the view. I do so, drawing upon a recent discussion of this issue by John Burgess, by explaining in detail the metaphysical position the proponent of the view should adopt in order to rebut the objection.     

Emergency Contraceptives and the Beginning of Human Animals

Emergency contraceptives may sometimes prevent implantation, thereby causing the death of the embryo. According to some positions contrary to abortion, because the embryo is a human animal, there are usually decisive moral reasons not to use them. In this article, I will show that objecting to the use of emergency contraceptives on those grounds is unjustified. If organisms are real existents, then according to the most plausible conception of what is required for a group of cells to compose one, the embryo cannot qualify as a single organism. On the other hand, if organisms are virtual objects, then whether or not the embryo qualifies as one is morally irrelevant. I conclude that even if those positions are right about the morality of abortion, they are not entitled to oppose the use of emergency contraceptives.     

The Effect of Elevated UV Radiation on Fucus spp. (Fucales,Phaeophyta) Zygote and Embryo Development

Abstract: This study has shown that in Fucus serratus and Fucus distichus, young zygotes and embryos are highly susceptible to elevated levels of both UVA (UVAR) and UVB radiation (UVBR). Zygotes treated with UVAR are able to polarise and germinate, but are very slow to divide; if they do, they often have skewed division planes or deformed rhizoids. Those treated with UVAR and UVBR remain spherical, they do not polarise, germinate to form rhizoids or undergo cell division. We suggest that the UVR may be affecting the cytoskeleton. Conversely, zygotes and embryos of Fucus spiralis are able to withstand these same UVR levels and, at the light microscope level, appear to develop normally. When the brown algal phenolic compound phloroglucinol was placed in a filter covering the developing embryos, normal development was seen under all treatments. Phenolic compounds protect the developing fucoids from UVR. In comparison with the other two species, Fucus spiralis grows high up on the shore and is exposed for much longer periods of time and, presumably, to higher levels of natural UVR. The failure of the juvenile stages of F. serratus and F. distichus to withstand UVR stress may have implications for the continued survival of these species in the intertidal, and may prove detrimental to the population as a whole if UVR levels increase.     

Life history patterns of new world monkeys

Allometric methods are used to investigate the life history patterns of New World monkeys. These patterns are compared to those found in other haplorhines and links with ecology are explored. The life history characteristics of the cebid monkeys suggest that these species are primarily slow breeding and slow developing for primates of their size. I suggest that these characteristics arose during a long period of adaptation to stable rainforest habitats. The capuchins and squirrel monkeys are a notable exception to the general rule that genera found outside primary forests will have a “fast” life history. In the marmosets and tamarins selection for small size and high birth rate has occurred, probably as a result of their adapting to more secondary habitats. It is this selection for rapid breeding, combined with the preadaptation of paternal care, that has probably led to twinning in these species. The evidence presented indicates that it is unlikely that twinning arose as a direct result of the mechanical constraints of small size but is more probably due to selection for increased reproductive output.     

A new definition of life

Chirality is often glossed over in theoretical or experimental discussions concerning the origin of life, but the ubiquity of homochiral building blocks in known biological systems demands explanation. Information theory can provide a quantitative framework for understanding the role of chirality in biology. Here I show how conclusions derived from information theory, in particular the concept of equivocation, can explain not only why chiral building blocks are necessary in living systems but also why a homochiral set of building blocks is necessary. These results lead to a new definition of life, and to the conclusion that the simplest form of life exists in the form of self-amplifying, autocatalytic reactions such as the Soai reaction.     

Biological transcomplementary activation as a novel and effective strategy applied to the generation of porcine somatic cell cloned embryos

A novel method termed the biological transcomplementary activation (B-TCA) has been recently utilized for the stimulation of porcine oocytes reconstituted by somatic cell nuclear transfer (SCNT). The use of cytosolic components originating from fertilized (FE) rabbit zygotes as the stimuli for the B-TCA of SCNT-derived pig oocytes appeared to be a highly efficient strategy applied to promote the in vitro development of cloned embryos, leading to a significant improvement in the blastocyst yield (43.6%) compared to the yields achieved using the standard protocol of simultaneous fusion and electrical activation (SF-EA; [31.3%]) or the protocol of delayed electrical activation (D-EA) independent of extracellular Ca²⁺ ions (0%). The FE rabbit zygote cytoplast-mediated B-TCA resulted in the increased blastocyst formation rate of porcine cloned embryos as compared to the B-TCA triggered by either cytoplasts isolated from pig parthenogenotes (PAs; [27.8%]) or rabbit PA-descended cytoplasts (0%). A considerably lower percentage of blastocysts containing apoptotic and/or necrotic (annexin V-eGFP-positive) cells were obtained from the SCNT-derived oocytes stimulated by the FE rabbit zygote cytoplast-based B-TCA (22.2%) compared to those stimulated using the SF-EA protocol (35.1%). In contrast to the B-TCA induced by FE rabbit zygote cytoplasts, apoptosis/necrosis incidence decreased totally among the cloned pig blastocysts that developed from reconstituted oocytes undergoing the porcine PA cytoplast-evoked B-TCA. In conclusion, the FE rabbit zygote cytoplast-mediated B-TCA turned out to be a relatively effective strategy for the in vitro production of porcine blastocyst clones of higher quality compared to those created using the standard SF-EA approach.     

Refining the ethics of preimplantation genetic diagnosis: A plea for contextualized proportionality

Many European countries uphold a ‘high risk of a serious condition’ requirement for limiting the scope of preimplantation genetic diagnosis (PGD). This ‘front door’ rule should be loosened to account for forms of PGD with a divergent proportionality. This applies to both ‘added PGD’ (aPGD), as an add‐on to in vitro fertilization (IVF), and ‘combination PGD’ (cPGD), for a secondary disorder in addition to the one for which the applicants have an accepted PGD indication. Thus loosening up at the front has implications at the back of PGD treatment, where a further PGD rule says that ‘affected embryos’ (in the sense of embryos with the targeted mutation or abnormality) should not be transferred to the womb. This ‘back door’ rule should be loosened to allow for transferring ‘last chance’ affected embryos in aPGD and cPGD cases, provided this does not entail a high risk that the child will have a seriously diminished quality of life.     

The pattern of cell wall adhesive formation by Fucus zygotes

As a first step in understanding the mechanism of algal adhesion, we describe the adhesive process during early development in Fucus gardneri zygotes. These brown algal embryos adhere to the intertidal substrate shortly after fertilization. Zygotes adhered nonspecifically to hydrophilic and hydrophobic substrates and microspheres. Initial binding of microspheres to the zygote surface coincided with initial zygote adhesion to the substrate. Binding of monodisperse dyed microspheres was used for adhesive localization and quantitation. The timing and extent of adhesive development were variable in populations of synchronously-fertilized zygotes. Small adhesive patches first appeared at 3–6 h, indicating secretion of adhesive components from cytoplasmic vesicles. The zygote hemisphere toward the substrate became sticky by 7–8 h. The entire surface was sticky after rhizoid germination at 12 h. Localization of adhesive at both the outer wall surface and along strands attached to the wall implicates cell wall polymers as a glue component. Loss of microspheres from the rhizoid surface in high salt or chelators indicates that initial adhesive attachment to the wall is noncovalent. Formation of adhesive aggregates in medium showed that the mechanism of adhesive formation includes two separable processes, secretion of adhesive components and extracellular interactions between adhesive components and the wall.     

Defining life from death: Problems with the somatic integration definition of life

To determine when the life of a human organism begins, Mark T. Brown has developed the somatic integration definition of life. Derived from diagnostic criteria for human death, Brown’s account requires the presence of a life-regulation internal control system for an entity to be considered a living organism. According to Brown, the earliest point at which a developing human could satisfy this requirement is at the beginning of the fetal stage, and so the embryo is not regarded as a living human organism. This, Brown claims, has significant bioethical implications for both abortion and embryo experimentation. Here, we dispute the cogency of Brown’s derivation. Diagnostic criteria for death are used to determine when an organism irreversibly ceases functioning as an integrated whole, and may vary significantly depending on how developed the organism is. Brown’s definition is derived from a specific definition of death applicable to postnatal human beings, which is insufficient for generating a general definition for human organismal life. We have also examined the bioethical implications of Brown’s view, and have concluded that they are not as significant as he believes. Whether the embryo is classified as a human organism is of peripheral interest—a far more morally relevant question is whether the embryo is a biological individual with an identity that is capable of persisting during development.     

生命科学新领域—组织工程

目前在生命科学研究的前沿领域出现了一门新的交叉学科－组织工程，本文拟向读者简要介绍有关组织工程的基本概念，主要研究内容以及国内外研究现状，着重介绍组织工程的三大研究要素：种子细胞，支架生物材料与细胞生长调节因子。     

Electron Probe Microanalysis of potassium and phosphorus in mouse oocytes and zygotes

Intracellular concentrations of potassium and phosphorus were determined by Electron Probe Microanalysis in mouse mature oocytes and zygotes. The oocytes were characterized by insignificant variations in the concentrations of these elements in the cytoplasm: 60 ± 4 and 103 ± 6 mM, respectively. In zygotes, on the contrary, significant variations were observed: 64 ± 16 and 84 ± 14 mM, respectively. Changes in the potassium homeostasis during the first cell cycle have been discussed.__________Translated from Ontogenez, Vol. 36, No. 2, 2005, pp. 123–127.Original Russian Text Copyright © 2005 by Pogorelov, Smolyaninova, Pogorelova, Goldstein.     

Molecules and mechanisms controlling the active DNA demethylation of the mammalian zygotic genome

The active DNA demethylation in early embryos is essential for subsequent development. Although the zygotic genome is globally demethylated, the DNA methylation of imprinted regions, part of repeat sequences and some gamete-specific regions are maintained. Recent evidence has shown that multiple proteins and biological pathways participate in the regulation of active DNA demethylation, such as TET proteins, DNA repair pathways and DNA methyltransferases. Here we review the recent understanding regarding proteins associated with active DNA demethylation and the regulatory networks controlling the active DNA demethylation in early embryos.     

Felicitometry: measuring the 'quality' in quality of life

Following Bernheim, ¹ 1 J.L. Bernheim. How to get serious answers to the serious question: ‘How have you been?’ Subjective quality of life (QOL) as an individual experiential emergent construct. Bioethics. 1998 ; 13 : 272 – 287 .
we examine aspects of ‘felicitometrics,’ ² 2 Jeremy Bentham (1748–1832) introduced the term ‘felicitometrics.’ He used the term ‘felicific calculus’ to describe methods for calculating the amounts of pleasure and pain consequent on particular courses of action: to wit, ‘Sum up all the values of all the pleasures on the one side and those of all the pains on the other. The balance, if it be on the side of pleasure, will give the good tendency of the act . . .’
the measurement of the ‘quality’ term in Quality of Life (QOL). Bernheim argued that overall QOL is best captured as the Gestalt ³ 3 Gestalts are unified wholes with the property that the arrangement of component features provides information not apparent in the features alone. The face provides an oft‐used example: Only by seeing the individual features of the face can one see the face as a whole, and only by seeing the face as a whole can one give meaning to its individual features.
of a global self‐assessment and suggested that the Anamnestic Comparative Self Assessment (ACSA) approach, in which subjects' memories of the best and worst times of their lives are used to anchor a Visual Analog Scale (VAS), provided a serious answer to the serious question, ‘How have you been?’ Bernheim compares and contrasts the ACSA to multi‐item questionnaire QOL instruments, such as the SF‐36, concluding that the ACSA has a number of advantages. His discussion assumes that the use of QOL outcomes in clinical trials is both relevant and appropriate. In the present paper, we document the reasonableness of this latter assumption, ⁴ 4 We emphasize that the choice of the outcome variable in clinical trials has ethical relevance, and that ethical considerations are paramount in choosing length of life and/or quality of life as primary, or at least secondary, outcomes.
contribute to the characterization of the similarities and differences between multi‐item and individualized QOL instruments, and point to some other individualized instruments that may be used in clinical trial contexts. These ‘other individualized instruments’ differ from the ACSA in fundamental ways; but they are individualized in that the subject defines those areas in his/her life that are most important, and these may vary from subject‐to‐subject.     

One hundred years of zygotic embryo culture investigations

Summary Isolation of zygotic embryos from seeds and their culture in a defined medium, initiated by Hanning in 1904, has proved to be a promising method to study the factors that control growth and differentiation of embryos. Using this technique, several investigations have focused on the carbohydrate and nitrogen nutrition during germination of cultured seed embryos and on the effects of plant hormones on their morphogenesis. Culture of immature embryos leads to their germination into weak seeldings, skipping the later stages of embryogenesis, by a process known as precocious germination. Progressively smaller embryos have been cultured by supplementation of the medium with coconut milk or hormonal additives or by osmotic adjustment of the medium by high concentrations of sucrose or mannitol. Although methods have not been developed for large-scale isolation and culture of zygotes, zygotes of maize isolated from embryo sacs and those obtained by in vitro fertilization have been grown in culture into full-term embryos. Embryo culture techniques are widely used to rescue embryos from seed of wide crosses which usually abort and to overcome dormancy of recalcitrant seeds.     

Open pulled straw (OPS) vitrification: A new way to reduce cryoinjuries of bovine ova and embryos

Although cryopreservation of certain mammalian embryos is now a routine procedure, considerable differences of efficiency exist depending on stage, species and origin (in vivo or in vitro produced). Factors that are suspected to cause most of these differences are the amount of the intracellular lipid droplets and the different microtubular structure leading to chilling injury as well as the volume/surface ratio influencing the penetration of cryoprotectants. A new approach, the Open Pulled Straw (OPS) method, which renders very high cooling and warming rates (over 20,000°C/min) and short contact with concentrated cryoprotective additives (less than 30 sec over −180°C) offers a possibility to circumvent chilling injury and to decrease toxic and osmotic damage. In this paper we report the vitrification by the OPS method of in vitro produced bovine embryos at various stages of development. Embryos cryopreserved from Day 3 to Day 7 (Day 0 = day of fertilization) exhibited development into blastocysts at rates equivalent to those of control embryos; even those cryopreserved on Day 1 or 2 exhibited only somewhat reduced survival. Eighty-one percent of Day 8 hatched blastocysts also survived the procedure. The method was also successfully used for bovine oocytes; of 184 vitrified oocytes, 25% developed into blastocysts after fertilization and culture for 7 days. Pregnancies were achieved following transfer after vitrification at both the oocyte and blastocyst stage. The OPS vitrification offers a new way to solve basic problems of reproductive cryobiology and may have practical impact on animal biotechnology and human assisted reproduction. Mol. Reprod. Dev. 51:53–58, 1998. © 1998 Wiley-Liss, Inc.     

A possible aid in targeted insertion of large DNA elements by CRISPR/Cas in mouse zygotes

The CRISPR/Cas system has rapidly emerged recently as a new tool for genome engineering, and is expected to allow for controlled manipulation of specific genomic elements in a variety of species. A number of recent studies have reported the use of CRISPR/Cas for gene disruption (knockout) or targeted insertion of foreign DNA elements (knock‐in). Despite the ease of simple gene knockout and small insertions or nucleotide substitutions in mouse zygotes by the CRISPR/Cas system, targeted insertion of large DNA elements remains an apparent challenge. Here the generation of knock‐in mice with successful targeted insertion of large donor DNA elements ranged from 3.0 to 7.1 kb at the ROSA26 locus using the CRISPR/Cas system was achieved. Multiple independent knock‐in founder mice were obtained by injection of hCas9 mRNA/sgRNA/donor vector mixtures into the cytoplasm of C57BL/6N zygotes when the injected zygotes were treated with an inhibitor of actin polymerization, cytochalasin. Successful germ line transmission of three of these knock‐in alleles was also confirmed. The results suggested that treatment of zygotes with actin polymerization inhibitors following microinjection could be a viable method to facilitate targeted insertion of large DNA elements by the CRISPR/Cas system, enabling targeted knock‐in readily attainable in zygotes. genesis 54:65–77, 2016. © 2016 Wiley Periodicals, Inc.