Low‐molecular‐weight (LMW) thiols are extensively involved in the maintenance of cellular redox potentials and the protection of cells from a variety of reactive chemical and electrophilic species. However, we recently found that the metabolic coupling of two LMW thiols – mycothiol (MSH) and ergothioneine (EGT) – programs the biosynthesis of the anti‐infective agent lincomycin A. Remarkably, such a constructive role of the thiols in the biosynthesis of natural products has so far received relatively little attention. (...) We speculate that the unusual thiol EGT might function as a chiral thiolation carrier (for modification) and a novel activator (for glycosylation) of sugar. Additionally, we examine recent evidence for LMW thiols (MSH and others) as sulfur donors of sulfur‐containing natural products. Clearly, the LMW thiols have more diverse activities beyond cell protection, and more attention should be paid to the correlation of their functions with thiol‐dependent enzymes. (shrink)

In this paper, rather than focusing on genes as an organising concept around which historical considerations of theory and practice in genetics are elucidated, we place genetic markers at the heart of our analysis. This reflects their central role in the subject of our account, livestock genetics concerning the domesticated pig, Sus scrofa. We define a genetic marker as a element existing in different forms in the genome, that can be identified and mapped using a variety of quantitative, classical and (...) molecular genetic techniques. The conjugation of pig genome researchers around the common object of the marker from the early-1990s allowed the distinctive theories and approaches of quantitative and molecular genetics concerning the size and distribution of gene effects to align in projects to populate genome maps. Critical to this was the nature of markers as ontologically inert, internally heterogeneous and relational. Though genes as an organising and categorising principle remained important, the particular concatenation of limitations, opportunities, and intended research goals of the pig genetics community, meant that a progressively stronger focus on the identification and mapping of markers rather than genes per se became a hallmark of the community. We therefore detail a different way of doing genetics to more gene-centred accounts. By doing so, we reveal the presence of practices, concepts and communities that would otherwise be hidden. (shrink)

In this paper, rather than focusing on genes as an organising concept around which historical considerations of theory and practice in genetics are elucidated, we place genetic markers at the heart of our analysis. This reflects their central role in the subject of our account, livestock genetics concerning the domesticated pig, Sus scrofa. We define a genetic marker as a element existing in different forms in the genome, that can be identified and mapped using a variety of quantitative, classical and (...) molecular genetic techniques. The conjugation of pig genome researchers around the common object of the marker from the early-1990s allowed the distinctive theories and approaches of quantitative and molecular genetics concerning the size and distribution of gene effects to align in projects to populate genome maps. Critical to this was the nature of markers as ontologically inert, internally heterogeneous and relational. Though genes as an organising and categorising principle remained important, the particular concatenation of limitations, opportunities, and intended research goals of the pig genetics community, meant that a progressively stronger focus on the identification and mapping of markers rather than genes per se became a hallmark of the community. We therefore detail a different way of doing genetics to more gene-centred accounts. By doing so, we reveal the presence of practices, concepts and communities that would otherwise be hidden. (shrink)

There is a widespread assumption that the classical work in philosophical semantics of Saul Kripke (1980) and Hilary Putnam (1975) has taught us that the essences of natural kinds of substances, such as water and gold, are discoverable only a posteriori by scientific investigation. It is such investigation, thus, that has supposedly revealed to us that it is an essential property of water that it is composed of H2O molecules. This is the way in which Scott Soames, in a recent (...) paper, makes the point in the case of water and H2O: [Here is] how a Kripkean explanation of the necessary a posteriority of [‘Water = H2O’] would go – or at any rate my version of it. The account holds that ‘water’ is a non-descriptive, directly-referential term designating a substance – where substances are taken to be physically constitutive kinds (instances of which share the same basic physical constitution). It is further assumed that a kind of this sort may have different instances in different world-states, and that if a and b are kinds with the same instances in all possible world-states, then a is b. These are clearly metaphysical assumptions, to which we add the natural corollary that for any substance, s, if, in some possible world-state, instances of s have a certain molecular structure, then instances of s have that structure in every world-state. In other words, we assume that it is an essential property of a substance that instances of it have the molecular structure they do. From this it follows that [‘Water = H2O’] is necessary if true, and that ‘H2O’– which I take to be equivalent to ‘the substance instances of which have a molecular structure with two hydrogen atoms and one oxygen atom’– is a rigid designator. Being true, [‘Water = H2O’] is, therefore, necessary. Since knowing the proposition it expresses requires knowing of a certain substance that its instances have a particular chemical structure, [‘Water = H2O’] is knowable only a posteriori. (Soames 2007: 36). (shrink)

‘Water is H2O’ is one of the most frequently cited sentences in analytic philosophy, thanks to the seminal work of Saul Kripke and Hilary Putnam in the 1970s on the semantics of natural kind terms. Both of these philosophers owe an intellectual debt to the empiricist metaphysics of John Locke's Essay Concerning Human Understanding, while disagreeing profoundly with Locke about the reality of natural kinds. Locke employs an intriguing example involving water to support his view that kinds (or ‘species’), such (...) as water and gold, are the workmanship of the human mind. This is the point of his story about a winter visitor to England from Jamaica, who is astonished to find that the water in his basin has turned solid overnight, and proceeds to call it ‘hardened water’. Locke criticizes this judgement, maintaining that it is more consonant with common sense to regard water and ice as different kinds of substance. Putnam, by implication, disagrees. Deploying his imaginary example of Twin Earth—a distant planet where a watery-looking substance, XYZ, rather than H2O, fills the oceans and rivers—he maintains that common sense supports the judgement that XYZ and H2O, despite their superficial similarity, are not the same kind of substance, precisely because their molecular compositions are different. Here it will be argued that both views are mistaken, but that, in this dispute, Locke has more right on his side than his modern opponents do. (shrink)

The aim of the paper is to prove the consistency of libertarianism. We examine the example of Jane, who deliberates at length over whether to vacation in Colorado (C) or Hawaii (H), weighing the costs and benefits, consulting travel brochures, etc. Underlying phenomenological deliberation is an indeterministic neural process in which nonactual motor neural states n(C) and n(H) corresponding to alternatives C and H remain physically possible up until the moment of decision. The neurophysiological probabilities pr(n(C)) and pr(n(H)) evolve continuously (...) according to the different weights Jane's judgement attaches to C and H at different times during the deliberation. The overall process is indeterministic, since Jane's exact judgemental weighting would vary slightly were the process to be repeated from the same initial conditions. The weighting is however rational, and entirely under Jane's control. This controlled, rational, indeterministic process shows that libertarianism is a consistent philosophical thesis. (shrink)

The aim of the paper is to prove the consistency of libertarianism. We examine the example of Jane, who deliberates at length over whether to vacation in Colorado (C) or Hawaii (H), weighing the costs and benefits, consulting travel brochures, etc. Underlying phenomenological deliberation is an indeterministic neural process in which nonactual motor neural states n(C) and n(H) corresponding to alternatives C and H remain physically possible up until the moment of decision. The neurophysiological probabilities pr(n(C)) and pr(n(H)) evolve continuously (...) according to the different weights Jane's judgement attaches to C and H at different times during the deliberation. The overall process is indeterministic, since Jane's exact judgemental weighting would vary slightly were the process to be repeated from the same initial conditions. The weighting is however rational, and entirely under Jane's control. This controlled, rational, indeterministic process shows that libertarianism is a consistent philosophical thesis. (shrink)

From the 1980s onwards, the Roslin Institute and its predecessor organizations faced budget cuts, organizational upheaval and considerable insecurity. Over the next few decades, it was transformed by the introduction of molecular biology and transgenic research, but remained a hub of animal geneticists conducting research aimed at the livestock-breeding industry. This paper explores how these animal geneticists embraced genomics in response to the many-faceted precarity that the Roslin Institute faced, establishing it as a global centre for pig genomics research (...) through forging and leading the Pig Gene Mapping Project (PiGMaP); developing and hosting resources, such as a database for genetic linkage data; and producing associated statistical and software tools to analyse the data. The Roslin Institute leveraged these resources to play a key role in further international collaborations as a hedge against precarity. This adoption of genomics was strategically useful, as it took advantage of policy shifts at the national and European levels towards funding research with biotechnological potential. As genomics constitutes a set of infrastructures and resources with manifold uses, the development of capabilities in this domain also helped Roslin to diversify as a response to precarity. (shrink)

In his paper ‘‘Bad luck once again’’ Neil Levy attacks our proof of the consistency of libertarianism by reiterating a time-worn compatibilist complaint.1 This is, that what is not determined must be due to chance. If A has a choice of X or Y, neither X nor Y being causally determined, then if A chooses X it can only be by chance, never for a reason. The only ‘‘reason’’ that could explain the choice of X over Y would have to (...) be a causally sufficient reason, which would rule out A’s having a genuine choice in the first place. Either X is causally necessitated or X is realized by sheer luck. But that these are the only alternatives is untrue. The exercise of deliberative reason opens the way between the Scylla of causal necessitation and the Charybdis of chance, as we shall try to make clear. The central core of Levy’s argument is that any attempt to give a reasons-based explanation of a contrastive fact must fail. A contrastive fact is a fact of the kind ‘‘Jane decides to vacation in Hawaii rather than Colorado,’’ or ‘‘Jane assigns a greater weight to surfing that to white-water rafting.’’ In the last three paragraphs of his paper Levy argues that Jane’s assigning more weight to surfing than to rafting cannot be a reasons-based assignment, because, as he puts it, ‘‘the reasons that would explain the weighting are the weighted reasons themselves.’’ Similarly, prior to making her Hawaii⁄ Colorado decision, Jane has.. (shrink)

Let T be a one-based theory. We define a notion of width, in the case of T having the finiteness property, for the lattice of finitely generated algebraically closed sets and prove Theorem. Let T be one-based with the finiteness property. If T is of bounded width, then every type in T is nonorthogonal to a weight one type. If T is countable, the converse is true.

Parvalbumins (PVs) are acidic, intracellular Ca2+‐binding proteins of low molecular weight. They are associated with several Ca2+‐mediated cellular activities and physiological processes. It has been suggested that PV might function as a “Ca2+ shuttle” transporting Ca2+ from troponin‐C (TnC) to the sarcoplasmic reticulum (SR) Ca2+ pump during muscle relaxation. Thus, PV may contribute to the performance of rapid, phasic movements by accelerating the contraction–relaxation cycle of fast‐twitch muscle fibers. Interestingly, PVs promote the generation of power stroke in fish (...) by speeding up the rate of relaxation and thus provide impetus to attain maximal sustainable speeds. However, immunological monitoring of diverse tissues demonstrated that PVs are also present in non‐muscle cells. The axoplasmic transport and various intracellular secretory mechanisms including the endocrine secretions seem to be controlled by the Ca2+ regulation machinery. Any defect in the Ca2+ handling apparatus may cause several clinical problems; for instance, PV deficiency alters the neuronal activity, a key mechanism leading to epileptic seizures. Moreover, atypical relaxation of the heart results in diastolic dysfunction, which is a major cause of heart failure predominantly among the aged people. PV may offer a unique potential to correct defective relaxation in energetically compromised failing hearts through PV gene transfer. Consequently, PV gene transfer may present a new therapeutic approach to correct cellular disturbances in Ca2+ signaling pathways of diseased organs. Hence, PVs appear to be amazingly useful candidate proteins regulating a variety of cellular functions through action on Ca2+ flux management. (shrink)

Low birth weight, intrauterine growth retardation, and prematurity are overwhelming risk factors associated with infant mortality and morbidity. The lack of efficacious prenatal screening tests for these three outcomes illuminates the problems inherent in bivariate estimates of association. A biocultural strategy for research is presented, integrating societal and familial levels of analysis with the metabolic, immune, vascular, and neuroendocrine systems of the body. Policy decisions, it is argued, need to be based on this type of biocultural information in order (...) to impact the difficult-to-change problems of low birth weight, intrauterine growth retardation, and prematurity. (shrink)

The aim of this study is an analysis of the possible adaptive consequences of delivery of low birth weight infants. We attempt to reveal the cost and benefit components of bearing small children, estimate the chance of the infants’ survival, and calculate the mothers’ reproductive success. According to life-history theory, under certain circumstances mothers can enhance their lifetime fitness by lowering the rate of investment in an infant and/or enhancing the rate of subsequent births. We assume that living in (...) a risky environment and giving birth to a small infant may involve a shift from qualitative to quantitative production of offspring. Given high infant mortality rates, parents will have a reproductive interest in producing a relatively large number of children with a smaller amount of prenatal investment. This hypothesis was tested among 650 Gypsy and 717 non-Gypsy Hungarian mothers. Our study has revealed that 23.8% of the Gypsy mothers had low birth weight (<2,500 g) children, whose mortality rate is very high. These mothers also had more spontaneous abortions and stillbirths than those with normal weight children. As a possible response to these reproductive failures, they shortened birth spacing, gaining 2–4 years across their reproductive lifespan for having additional children. Because of the relatively short interbirth intervals, by the end of their fertility period, Gypsy mothers with one or two low birth weight infants have significantly more children than their ethnic Hungarian counterparts. They appear to compensate for handicaps associated with low birth weights by having a larger number of closely spaced children following the birth of one or more infants with a reduced probability of survival. The possible alternative explanations are discussed, and the long-term reproductive benefits are estimated for both ethnic groups. (shrink)

Retinoids are low molecular weight, lipophilic derivatives of vitamin A which have a profound effect upon the development of a diverse array of animals. Here, I review these effects on Invertebrates: a colonial hydroid, a colonial ascidian, and Vertebrates: the regenerating amphibian limb, the developing chick limb bud, the regenerating amphibian tail, the anteroposterior axis of the early embryo, the developing chick embryo skin. There is a striking uniformity of effect of retinoids on pattern formation when applied to (...) these diverse organisms. The majority react by being posteriorized in their development, although additional effects can also be seen. Several hypotheses which can explain these results are discussed along with the deduction that they lead to: retinoids may be components of a universal developmental mechanism or they may simply act in a similar way to alter a universal developmental mechanism. In either case the experimental analysis of retinoid effects on development has important implications for the evolution of developmental mechanisms. (shrink)

S100 protein is a low molecular weight calcium‐binding protein widely distributed in the central nervous system of vertebrates. Recent evidence suggests that S100 protein may play a role in the regulation of glial proliferation and neuronal differentiation. The gene for S100 protein has been mapped to the 21q22 region, a chromosomal locus whose duplication has been implicated in the generation of Down Syndrome (DS). This raises the possibility that abnormalities in S100 protein gene dosage at a critical period (...) during development may be responsible for some of the neurologic abnormalities associated with DS. (shrink)

Background: Cancer patients are at risk of developing blood clots in their veins - venous thromboembolism(VTE) - which often takes the form of a pulmonary embolism or deep vein thrombosis. Therisk increases with advanced disease. Evidence based treatment is low molecular weightheparin (LMWH) by daily subcutaneous injection. The aim of this research is to explore thebarriers for doctors in the UK when diagnosing and treating advanced cancer patients withVTE.MethodQualitative, in-depth interview study with 45 doctors (30 across Yorkshire, England and (...) 15across South Wales). Doctors were from three specialties: oncology, palliative medicine andgeneral practice, with a mixture of senior and junior staff. Framework analysis was used. Results: Doctors opinions as to whether LMWH treatment was ethically appropriate for patients whowere symptomatic from VTE but at end of life existed on a shifting continuum, largelyinfluenced by patient prognosis. A lack of immediate benefit coupled with the discomfort of adaily injection had influenced some doctors not to prescribe LMWH. The point at whichLMWH injections should be stopped in patients at the end of life was ambiguous. Someperceived overcaution in their own and other clinicians treatment of patients. Viewpointswere divergent on whether dying of a PE was considered a "good way to go". Theinterventionalism and ethos of palliative medicine was discussed. Conclusions: Decisions are difficult for doctors to make regarding LMWH treatment for advanced cancerpatients with VTE. Treatment for this patient group is bounded to the doctors own moral andethical frameworks. (shrink)

RESUMEN La problemática del muy bajo peso al nacer ha sido abordada desde hace varios años, sin embargo, las investigaciones están enfocadas desde diferentes perspectivas y contextos, no siempre se ha considerado su repercusión a corto y a largo plazo, así como la interacción de los diferentes factores que se relacionan con este riesgo biológico. Por ello en esta revisión bibliográfica se realiza una valoración de estudios ejecutados a nivel internacional y en Cuba dedicados al desarrollo neuropsicológico de niños con (...) muy bajo peso al nacer. Se concluye que el muy bajo peso al nacer repercute en el desarrollo neuropsicológicos desde edades tempranas, hasta la adolescencia; por ello es necesario una visión integradora que tenga en cuenta el riesgo biológico, las particularidades individuales y el contexto social en que se desenvuelve el niño desde los primeros momentos, lo que posibilitará, perfeccionar la atención a corto y largo plazo al grupo de riesgo. ABSTRACT The problems of very low birth weight have been dealt with for many years, however, research on the matter is approached from different perspectives and contexts, not always have its short and long term repercussions being considered as well as the interaction of different factors related to this biological risk. Therefore, this bibliographical review makes an assessment of international and Cuban studies devoted to very low birth weight children’s neuropsychological development. It was reached the conclusion that very low birth weight affects neuropsychological development from early ages to adolescence; for that reason, it is necessary to have an integrated approach of the problem that takes into account the biologicals risk, individual characteristics and the social context in which the child develops from the beginning, which will make the improvement of short and long term care to this risk group possible. (shrink)

Movement of leukocytes from peripheral blood into tissues, also called leukocyte extravasation, is absolutely essential for immunity in higher organisms. Over the past decade, our understanding of the molecular mechanisms involved in white blood cell extravasation during both normal immune surveillance and the generation of protective immune responses has taken a great leap forward with the discovery of the chemokine gene superfamily. Chemokines are low-molecular-weight cytokines whose major collective biological activity appears to be that of chemotaxis of (...) both specific and overlapping subsets of leukocytes. They are therefore likely to play a critical role in the directed movement of leukocytes from the bloodstream into tissue. These molecules are almost exclusively secreted and act as extracellular messengers for the immune system. However, emerging data also show that various members of the chemokine gene superfamily exert other biological effects outside the immune system. All nucleated cells and all tissues examined to date are capable of expressing at least some chemokines, and it seems likely therefore that by the time all the chemokines are identified, and all their biological functions elucidated, we will find that, as a family, these molecules perform an extracellular messenger role in all tissues and systems of the body. BioEssays 1999;21:17–28. © 1999 John Wiley & Sons, Inc. (shrink)

High‐molecular‐weight hyaluronan acts as a ligand of the tumor‐suppressive Hippo signal, whereas degradation of hyaluronan from a high‐molecular‐weight form to a low‐molecular‐weight forms by hyaluronidase 2 inhibits Hippo signal activation and thereby activates the pro‐oncogenic transcriptional coactivator yes‐associated protein (YAP), which creates a cancer‐predisposing microenvironment and drives neoplastic transformation of cells through both cell‐autonomous and non‐cell‐autonomous mechanisms. In fact, accumulation of low‐molecular‐weight hyaluronan in tissue stroma is observed in many types of cancers. (...) Since inhibition of YAP activity suppresses tumor growth in vivo, pharmacological intervention of the Hippo‐YAP signal is an attractive approach for future drug development. In this review, pharmacological intervention of excessive hyaluronan degradation as a novel approach for inhibition of the Hippo‐YAP signal is also discussed. Development of hyaluronidase inhibitors may provide novel therapeutic strategies for human malignant tumors. (shrink)

Flavonoids are a class of low molecular weight phenolic compounds that is widely distributed in the plant kingdom. They exhibit a diverse spectrum of biological functions and play an important role in the interaction between plants and their environment. Flavonoids not only protect the plant from the harmful effects of UV irradiation but also play a crucial role in the sexual reproduction process. A special class of flavonoid polymers, the tannins, plays a structural role in the plant. Yet (...) other classes of flavonoids, flavonols and anthocyanins, have been implicated in the attraction of pollinators. Certain flavonoids participate in the interaction between plants and other organisms such as symbiotic bacteria and parasites. This raises the intriguing question as to how these different compounds arose and evolved. Based on taxonomy and molecular analysis of gene expression patterns it is possible to deduce a putative sequence of acquisition of the different branches of the biosynthetic pathway and their regulators. (shrink)

Background Cancer patients are at risk of developing blood clots in their veins - venous thromboembolism - which often takes the form of a pulmonary embolism or deep vein thrombosis. The risk increases with advanced disease. Evidence based treatment is low molecular weight heparin by daily subcutaneous injection. The aim of this research is to explore the barriers for doctors in the UK when diagnosing and treating advanced cancer patients with VTE. Method Qualitative, in-depth interview study with 45 (...) doctors. Doctors were from three specialties: oncology, palliative medicine and general practice, with a mixture of senior and junior staff. Framework analysis was used. Results Doctors opinions as to whether LMWH treatment was ethically appropriate for patients who were symptomatic from VTE but at end of life existed on a shifting continuum, largely influenced by patient prognosis. A lack of immediate benefit coupled with the discomfort of a daily injection had influenced some doctors not to prescribe LMWH. The point at which LMWH injections should be stopped in patients at the end of life was ambiguous_._ Some perceived ‘overcaution’ in their own and other clinicians’ treatment of patients_._ Viewpoints were divergent on whether dying of a PE was considered a “good way to go”. The interventionalism and ethos of palliative medicine was discussed. Conclusions Decisions are difficult for doctors to make regarding LMWH treatment for advanced cancer patients with VTE. Treatment for this patient group is bounded to the doctors own moral and ethical frameworks. (shrink)

The prenylated proteins represent a newly discovered class of post‐translationally modified proteins. The known prenylated proteins include the oncogene product p21ras and other low molecular weight GTP‐binding proteins, the nuclear lamins, and the γ subunit of the heterotrimeric G proteins. The modification involves the covalent attachment of a 15‐carbon (farnesyl) or 20‐carbon (geranylgeranyl) isoprenoid moiety in a thioether linkage to a carboxyl terminal cysteine. The nature of the attached substituent is dependent on specific sequence information in the carboxyl (...) terminus of the protein. In addition, prenylation entrains other post‐translational modifications forming a reaction pathway. In this article, we review our current understanding of the biochemical reactions involved in prenylation and discuss the possible role of this modification in the control of cellular functions such as protein maturation and cell growth. (shrink)

This study investigates the possible effects of pre-term births and low birth weight on infant mortality rates (IMRs) over a 15-year period in Ribeirão Preto, Brazil, based on surveys carried out in 1978/79 and 1994. The 1978/79 survey included 6750 births over a 12-month period and the 1994 survey 2846 births over a 4-month period. Infant deaths were retrieved monthly from the city register. Infant mortality rate decreased from 36·6 to 16·9 deaths per 1000 over 15 years. The decrease (...) in IMR was larger in the 25000·63); it increased to 0·57 (95% CI 0·350·97) when adjusted for length of gestation and other variables. The increase in pre-term births and low birth weight may have had, at most, a marginal effect on the IMR. Progress in the care of newborns may have decreased the mortality risk, but even mild pre-term birth still has an impact on infant mortality. There is room for further improvement in IMR by tackling the high rates of pre-term birth. (shrink)

Plants growing in temperate regions are able to survive freezing temperatures from −5° to −30°C, depending on the species, through a process known as cold acclimation. In the last decade much work has been done on the molecular mechanisms of low temperature (LT) signal transduction and cold acclimation. Mutant studies and microarray analyses have revealed C-Repeat binding factor (CBF) -dependent and -independent signaling pathways in plants. Experimental evidence suggests the existence of ‘potential LT sensors’ but as yet there is (...) no direct proof. A number of signal transducers such as various kinases/phosphatases have been demonstrated but the signal transduction pathways have not been elucidated. An understanding of the molecular basis of the signaling process, however, is of potential practical application. Designing new strategies to improve cold tolerance in crop varieties could increase the plant productivity and also expand the area under cultivation. BioEssays 27:1048–1059, 2005. © 2005 Wiley Periodicals, Inc. (shrink)

In normal human cells, a protein with a molecular weight of about 53,000 (p53) is present at a low level, detectable only by sensitive assays. When the cells are infected with some DNA tumour viruses or transformed by the same viruses, the amount of this protein increases dramatically, and much of it is found in a physical association with the virus‐coded protein that causes the transformation. The increase in amount and, incidentally, stability of p53 is not peculiar to (...) virus‐transformed cells, but also occurs in cells transformed by chemicals or radiation where there is no sign of any virus being involved (reviewed by Crawford).1 Cells in culture are not the same as cells in a patient, but these observations do raise questions about the possible involvement of p53 in human tumours. (shrink)

Development of biopharmaceuticals is a challenging issue in bioethics. Unlike conventional, small molecular weight drugs, biopharmaceuticals are proteins derived from DNA technology and hybrid techniques with complex three dimensional structures. Immunogenicity of biopharmaceuticals should always be tested in clinical settings due to low predictive value of preclinical animal models. However, non-human primates and transgenic mice could be used to address certain aspects of immunogenicity. Substantial efforts have been made to reduce NHP use in biopharmaceutical drug development, e.g. study (...) design improvements and changes in regulatory policy. In addition, several expert groups are active in this field. Despite that, there is an increasing trend of use of NHP in preclinical safety testing of biopharmaceuticals, especially regarding monoclonal antibodies. Other potential bioethical issues related biopharmaceutical drug development are their cost/effectiveness ratio, clinical safety assessment, production of biosimilars, and comparison of their efficacy with placebo in countries without intention to market. Identification of the human genome has opened many new bioethical issues. Development of biopharmaceuticals is an important bioethical issue for several reasons. It connects all aspects of contemporary bioethics: bio?medicine, animal welfare and the most recent ad?vances in biotechnology. In particular, biopharmaceutical drug development is a challenging issue regarding treatment of rare diseases. Razvoj biofarmaceutika predstavlja izazov u bioetici. Za razliku od uobicajenih lekova male molekulske mase, biofarmaceutici su proteini kompleksne trodimenzionalne strukture koji se dobijaju tehnologijom rekombinantne DNK i tehnikom hibridoma. Imunogenost biofarmaceutika treba uvek proveriti u klinickim studijama zbog male prediktivne prednosti pretklinickih animalnih modela. Medjutim, primati i transgeni sojevi miseva mogu se upotrebiti da bi se naznacili neki aspekti imunogenosti. Znacajni napori su ucinjeni u cilju smanjenja upotrebe primata u razvoju biofarmaceutika, npr. poboljsanja dizajna istrazivanja i promene u zakonskoj regulativi. Osim toga, u ovoj oblasti su aktivne i pojedine ekspertske grupe. Uprkos tome, postoji rastuci trend upotrebe primata izuzev coveka u pretklinickom ispitivanju bezbednosti biofarmaceutika, posebno kada su u pitanju monoklonska antitela. Druga bioeticka pitanja koja se mogu dovesti u vezu sa razvojem biofarmaceutika su odnos njihove cene i efikasnosti, procena bezbednosti u klinickim uslovima, proizvodnja bioloski slicnih lekova i uporedjivanje njihove efikasnosti sa placebom u zemljama u kojima ne postoji namera o plasmanu. Upoznavanje humanog genoma otvorilo je mnoga bioeticka pitanja. Razvoj biofarmaceutika je vazno bioeticko pitanje iz vise razloga. Ono povezuje sve aspekte savremene bioetike: biomedicinu, dobrobit zivotinja i najnovija dostignuca u biotehnologiji. Posebno, razvoj biofarmaceutika je izazov kada je u pitanju lecenje retkih bolesti. (shrink)

The main aim of the paper is to reinforce the notion that emergence is a basic characteristic of the molecular sciences in general and chemistry in particular. Although this point is well accepted, even in the primary reference on emergence, the keyword emergence is rarely utilized by chemists and molecular biologists and chemistry textbooks for undergraduates. The possible reasons for this situation are discussed. The paper first re-introduces the concept of emergence based on very simple geometrical forms; and (...) considers some simple chemical examples among low and high molecular weight compounds. On the basis of these chemical examples, a few interesting philosophical issues inherent to the field of emergence are discussed – again making the point that such examples, given their clarity and simplicity, permit one to better understand the complex philosophical issues. Thus, the question of predictability is discussed, namely whether and to what extent can emergent properties be predicted on the basis of the component’s properties; or the question of the explicability (a top down process). The relation between reductionism and emergentism is also discussed as well as the notion of downward causality and double causality (macrodeterminism); namely the question whether and to what extent the emergent properties of the higher hierarchic level affect the properties of the lower level components. Finally, the question is analyzed, whether life can be considered as an emergent property. More generally, the final point is made, that the re-introduction of the notion of emergence in chemistry, and in particular in the teaching, may bring about a deeper understanding of the meaning of chemical complexity and may bring chemistry closer to the humanistic areas of philosophy and epistemology. (shrink)

In this article, we use qualitative methodology to explore how 15 low‐income women of diverse sociocultural location construct and experience health and weight gain during pregnancy, as well as how they position themselves in relation to messages pertaining to weight gain, femininity and motherhood that they encounter in their lives. Discussing the findings through a feminist poststructuralist lens, we conclude that the participants are complex, fragmented subjects, interpellated by multiple and at times conflicting subject positions. While the discourse (...) of maternal responsibility (i.e. managing personal behaviours for the baby's health) is very much in evidence in their narratives, embodied experiences of pregnancy, lived experiences of financial constraints and religious beliefs provided some with an alternative discourse and resistant subject position. Participants also had mixed emotions about weight gain; they recognized the need to gain weight in order to have a healthy pregnancy, but weight gain was also not welcome as participants reproduced the dominant discourse of obesity and the discourse of ‘feminine’ bodily norms. Based on our results, we advocate for change to recent clinical guidelines and social discourses around pregnancy and weight gain, as well as for policies that provide pregnant women with a range of health‐promoting resources. (shrink)

Probability weighting is a marked feature of decision-making under risk. For poor people in rural areas of developing countries, how probabilities are evaluated matters for livelihoods decisions, especially the probabilities associated with losses. Previous studies of risky choice among poor people in developing countries seldom consider losses and do not offer a refined tracking of the probability-weighting function. We investigate probability weighting among smallholder farmers in Uganda, separately for losses and for gains, using a method that allows refined tracking of (...) the PWF for a population with low levels of literacy. For losses, we find marked probability weighting near zero, which is in line with evidence found in Western labs. For gains, the absence of probability weighting is remarkable, particularly its absence near 100%. We also find marked differences in probability weighting for traditional farmers which are in line with the observed livelihoods strategies in the study area. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:The Weight I Just Can’t LoseShelley Lynn MeyersI have always been a “fat person”. According to the medical definition though, I have not always been obese. I have spent most of my life on a journey from chubby to obese, finally ending at my current “overweight” status. After years of struggling with obesity I had gastric bypass surgery, finally losing enough weight to be “normal.” However, regardless (...) of the number on the scale or the BMI category into which I fell, I was still “fat”. I may have lost weight but I did not lose the experience and memories of life as an obese person. I was a fat girl on the inside.My earliest memories of childhood consist of feeling fat and awkward. I was the kid reading a book, watching other little girls practice their cartwheels and boys play tag. I was the kid who also hated gym class, especially the days we practiced tumbling or had to climb ropes. I heard the other kids laugh when I had difficulty doing these things. It’s no surprise that I was last or next to last when we had to choose teams for sports. At least when we played flag football I could play center and use my weight as an asset, blocking players from the other team.Certainly, taunts about my weight and even my own intrusive condemning thoughts were not constant, but they were frequent. Admittedly, I probably berated myself much more often than my peers did. I hated being different. What saddens me to this very day are promises I would make to God if I only I could be “like everyone else”. Oh the things that I would change, or give up for the gift of being a normal size. Even my good qualities, such as academic achievement, became another characteristic that made me stand out when all I wanted to do was hide amongst the crowd. I would have happily traded the high GPA for a lower number on the scale. [End Page E4]Some memories from that era seem to be forever etched into my mind. It has been more than thirty years since I was in the seventh grade, but I remember one particular incident very clearly. I went to my first school dance and was thrilled that I actually slow danced with a boy that I had liked since the fourth grade, Jeff1*. We danced to “How Much I Feel” by Ambrosia. Jeff wore a plaid flannel shirt, and I remember how soft it felt when I put my arms around his neck. The puppy love joy I felt that night was short-lived. At school the next day I read a note written by a female classmate. She wrote about the dance, saying that she had wanted to dance with Jeff, but “he was dancing with that fat pig”. She included my name as well, so there was no mistaking to whom she was referring. I felt nauseous. I decided that happiness was just a set-up for disappointment.Even though I thinned out somewhat during high school, I was still larger than most of my friends and saw myself as fat. I received few actual comments about my weight but I just knew they were thinking it. My best friends were exceptionally thin (one, I would later find out had an eating disorder), which added to my distorted body image. I also was the “friend”, rather than the “girlfriend”, with boys asking me to introduce them to my skinny friends. I was ecstatic when I had a horrible case of the flu and lost a lot of weight due to vomiting and the inability to keep food down. I remember hoping that I could get the flu every couple of months.I read fashion magazines and studied the latest, greatest ways to lose weight. Diet pills, fad soup diets and low calorie frozen dinners were popular and I tried most of them. Sadly, the very methods I tried to “get skinny” likely put me on the path to obesity. Starving myself just led to unhealthy eating, cravings and quite possibly, a metabolism that had no... (shrink)

In Western society, weight moralization is reflected in the belief that weight is controllable across the weight spectrum. However, the effect of holding such beliefs is unclear. We therefore propose that these beliefs affect people differently depending on their BMI. When confronted with negative, self-related feedback, people’s coping strategies are often reflected in the ways they relate to their self. We examine three such self-to-self relations (i.e., reassured, inadequate, and hated self). Extending prior research, we predict that (...) weight controllability beliefs are related to positive self-to-self relations for adults with a low, and to negative self-to-self relations for adults with a high BMI. Accordingly, we expected that weight controllability beliefs would be associated with defensive avoidance among people with a high, but not with a low BMI. We tested our hypotheses in a sample of 348 adults who participated in an online survey. Weight controllability beliefs were associated with increased defensive avoidance in people with high BMI, and with decreased defensive avoidance in adults with a low BMI. Forms of self-to-self relating fully mediated this association, demonstrating positive effects on adults with a low, and negative effects on adults with a high BMI. Additionally, in an open ending section, we found seven social settings that deprive people from satisfying their need to belong and to be accepted due to their weight. We discuss our findings against a call for a less moralized public discourse about overweight and obesity that is particularly relevant in the context of the current COVID-19 pandemic. (shrink)