Chromatin structure and dynamics regulate key cellular processes such as DNA replication, transcription, repair, remodeling, and gene expression, wherein different protein factors interact with the nucleosomes. In these events, DNA and RNA polymerases, chromatin remodeling enzymes and transcription factors interact with nucleosomes, either in a DNA‐sequence‐specific manner and/or by recognizing different structural features on the nucleosome. The molecular details of the recognition of a nucleosome by different viral proteins, remodeling enzymes, histone post‐translational modifiers, and RNA polymerase II, have been explored (...) in the recent past. The present review puts forth critical insights into the basic mechanisms of nucleosome recognition by the various protein factors and the role of distinct surface epitopes on a nucleosome. These determinants of the underlying specificity include features such as the acidic patch, arginine anchor, histone post‐translational modifications, core DNA, DNA lesions, and linker DNA. (shrink)

Flap EndoNuclease‐1 (FEN‐1) is a multifunctional and structure‐specific nuclease involved in nucleic acid processing pathways. It plays a critical role in maintaining human genome stability through RNA primer removal, long‐patch base excision repair and resolution of dinucleotide and trinucleotide repeat secondary structures. In addition to its flap endonuclease (FEN) and nick exonuclease (EXO) activities, a new gap endonuclease (GEN) activity has been characterized. This activity may be important in apoptotic DNA fragmentation and in resolving stalled DNA replication forks. The (...) multiple functions of FEN‐1 are regulated via several means, including formation of complexes with different protein partners, nuclear localization in response to cell cycle or DNA damage and post‐translational modifications. Its functional deficiency is predicted to cause genetic diseases, including Huntington's disease, myotonic dystrophy and cancers. This review summarizes the knowledge gained through efforts in the past decade to define its structural elements for specific activities and possible pathological consequences of altered functions of this multirole player. BioEssays 27:717–729, 2005. © 2005 Wiley Periodicals, Inc. (shrink)

A photoaffinity analog of cGMP has been used to biochemically identify a new ligand-binding subunit of the retinal rod cGMP-activated ion channel, as well as amino acids in contact with cGMP in the original subunit. Covalent tethering of this probe to channels in excised menbrane patches has revealed a functional heteogeneity in the ligand-binding sites that may arise from the two biochemically identified subunits.

Over the past three decades the ethnographic-based human sciences (anthropology, social linguistics, ethnomusicology, sociology, etc.) have come under heavy scrutiny for the perpetuation of injustice and inequality, and a lack of sensitivity to indigenous epistemologies and material needs. Among the nefarious epistemological issues is that of “transcendental knowledge,” information that is presented as “fact” or through impervious narrative in the mode of so-called empirical sciences. The model of transcendental knowledge still pervades the human sciences despite critiques from postcolonial and poststructural (...) scholars. Through a simultaneous re-evaluation of the Dialectic of Enlightenment 's critique and an analysis of the pressures and perils of the academic market, we can see how Horkheimer and Adorno's cautionary analysis can be applied to contemporary ethnography in an effort to philosophize and practice writing that does not submit to the reifying pressures of grand and grave theories and represents human life with the deserved dignity and distress. (shrink)

Qualitative inquiry into eating disorders is burgeoning, offering valuable and innovative insights into various aspects of the condition. This study used life‐history interviews with 20 women who had recovered from anorexia nervosa, bulimia nervosa or both and who had remained healthy. The interviews focused on the women's narratives and experience rather than a diagnostic therapeutic model. Three themes of control, connectedness and conflict emerged as significant in the development, experience of, and recovery from an eating disorder. The development of the (...) condition was attributed to a lack of control, a sense of non‐connectedness to family and peers and extreme conflict with significant others. Recovery occurred when the women re‐engaged with life, developed skills necessary for conflict resolution and rediscovered their sense of self. Rather than viewing the development of, and recovery from an eating disorder as separate and discrete events, the data from the life‐history interviews suggest they are better viewed as one entity — that is, the journey of an individual attempting to discover and develop their sense of self. This perspective challenges some current constructs of eating disorders; it is not a condition in and of itself but a symptom of deeper issues that if addressed, when the individual is ‘ready’ to make that choice, will lead to recovery. (shrink)

This book provides journalism students with an easy-to-read yet theoretically rich guide to the dialectics, contradictions, problems, and promises encapsulated in the term 'journalism ethics'. Offering an overview of a series of crises that have shaken global journalism to its foundations in the last decade, including the Coronavirus pandemic, the Black Lives Matter movement, and the 2020 US presidential election, the book explores the structural and ethical problems that shape the journalism industry today. The authors discuss the three principle existential (...) crises that continue to plague the news industry: a failing business model, technological disruption, and growing public mistrust of journalism. Other topics covered include social media ethics, privacy concerns, chequebook journalism, as well as a new analysis of journalism theory that critiques the well-worn tropes of objectivity, the Fourth Estate, freedom of the press, and the marketplace of ideas to develop a sophisticated materialist reimagining of journalism ethics. This is a key text for students of journalism, mass communication, and media ethics, as well as for academics, researchers, and communications professionals interested in contemporary journalism ethics. (shrink)

ExcerptNow a century old, Carl Schmitt’s The Crisis of Parliamentary Democracy still provides useful training for historians in the necessary task of making distinctions between “liberalism” and “democracy,” two movements that arose with overlapping but distinct core principles in eighteenth-century Europe, often competed with each other, and sometimes came into bloody conflict. Schmitt makes one highly controversial assertion, however, near the beginning of this book. After agreeing with Alexis de Tocqueville that the spread of democracy was the most powerful political (...) trend of the nineteenth century, a trend that became almost irresistible,1 Schmitt declares that there is a crucial flaw in the argument of Jean-Jacques Rousseau that exposes a major problem with democratic theory in general. Democracy has taken so many different forms, according to Schmitt, that it can only be defined according to the basic principle that political decisions are only binding for those who participated in making them. This belief presupposes “that the will of the outvoted minority is in truth identical with the will of the majority. Rousseau’s frequently cited arguments in the Contrat social are fundamental [emphasis added] for democratic thought and ultimately conform to an old tradition.”2 Schmitt refers here to Rousseau’s argument in On the Social Contract (book IV, ch. 2) that if the proposition you supported fails to gain a majority in a referendum, you should acknowledge that you had been mistaken when you voted, because the question posed to citizens was not exactly whether they personally approved of the proposition, but “whether or not it conforms to the general will that is theirs.”3 Schmitt observes caustically that “with this Jacobin logic one can, it is well known, justify the rule of a minority over the majority, even while appealing to democracy.” The first democratic movement of the modern era, the Levellers in the English Civil War, had already attempted this, Schmitt argues, when they proclaimed in 1649 that only the “well-affected” deserved the right to vote in parliamentary elections.4 Schmitt concludes that democracy is therefore highly vulnerable to the emergence of dictatorship, and that the Bolsheviks had just as strong an argument in 1923 that their brutal dominion by an “enlightened” minority was truly democratic as did the Jacobins of 1793. “Theoretically, and in critical times also practically, democracy is helpless [emphasis added] before the Jacobin argument, that is, when faced with the authoritative identification of a minority as the people.” The meaning here of “authoritative identification” (entscheidenden Identifikation) is unclear; Schmitt does not seek to explain why the majority in a democracy should ever accept a minority’s claim that it alone possesses civic virtue or wisdom.5 A very similar argument about Rousseau was made nevertheless by J. L. Talmon in The Origins of Totalitarian Democracy (published in 1952), which has in turn influenced some recent scholars who, like Talmon, do not acknowledge any intellectual debt to Schmitt.6. (shrink)

Drawing on a survey of over 4000 students and 1300 faculty members at the University of Maryland Global Campus, we find evidence for a reconceptualization of the use of commercialized websites offering access to “tutors” or “study help” as a type of collaborative cheating. Past studies have examined this behavior as an extension of contract cheating, but we find that students perceive the use of these sites very differently than they perceive contract cheating behaviors. In this paper we will discuss (...) how “tutor” or “study helper” websites combine the phenomena of collaborative cheating with internet-driven shifts in cultural and social perceptions to create a new type of cheating behavior that is viewed differently by students and faculty. (shrink)

Psychedelics such as psilocybin reliably produce significantly altered states of consciousness with a variety of subjectively experienced effects. These include certain changes to perception, cognition, and affect,1 which we refer to here as the acute subjective effects of psychedelics. In recent years, psychedelics such as psilocybin have also shown considerable promise as therapeutic agents when combined with talk therapy, for example, in the treatment of major depression or substance use disorder.2 However, it is currently unclear whether the aforementioned acute subjective (...) effects are necessary to bring about the observed therapeutic effects of psilocybin and other psychedelics. This uncertainty has sparked a lively—though still largely hypothetical—debate on whether psychedelics without subjective effects (“nonsubjective psychedelics” or “non-hallucinogenic psychedelics”) could still have the same therapeutic impact, or whether the acute subjective effects are in fact necessary for this impact to be fully realized.3,4,5. (shrink)

The Covid-19 pandemic has demonstrated the potential of genomic technologies for the detection and surveillance of infectious diseases. Pathogen genomics is likely to play a major role in the future of research and clinical implementation of genomic technologies. However, unlike human genetics, the specific ethical and social challenges associated with the implementation of infectious disease genomics has received comparatively little attention. In this paper, we contribute to this literature, focusing on the potential consequences for individuals and communities of the use (...) of these technologies. We concentrate on areas of challenges related to privacy, stigma, discrimination and the return of results in the cases of the surveillance of known pathogens, metagenomics and host genomics. (shrink)

Volume 24, Issue 7, July 2024, Page 6-12.

Refining the model for an emergency department‐based mental health nurse practitioner outpatient service The mental health nurse practitioner (MHNP) role based in the emergency department (ED) has emerged in response to an increase in mental health‐related presentations and subsequent concerns over waiting times, co‐ordination of care and therapeutic intervention. The MHNP role also provides scope for the delivery of specialised primary care. Nursing authors are reporting on nurse‐led outpatient clinics as a method of healthcare delivery that allows for enhanced access (...) to health‐care, particularly following hospital discharge. However, due to a lack of in‐depth substantiation, this mode of service delivery requires more thorough investigation. This study describes the refinement phase undertaken before the implementation and pilot evaluation of a formalised and structured MHNP outpatient service in the ED of a large inner‐city hospital in Sydney, Australia. An expert advisory panel (EAP) consisting of key local informants was convened to provide feedback on and refinement to the proposed model. This related to issues such as target population, structure and process considerations, outcome measures and interface within the overall health service. Findings from the EAP meeting are presented and discussed. The importance of linking methods with the appropriate methodology in evaluating a healthcare program is highlighted. (shrink)

When used clinically, psychedelics may appear unusual or even unique when compared to more familiar or long-standing medical interventions, prompting some to suggest that the ethical issues raised may likewise be exceptional. If that is correct, then perhaps psychedelics should be treated differently from other medical substances: for example, by being subjected to different ethical or evidentiary standards. Alternatively, it may be that psychedelics have more in common with various existing medical interventions than first meets the eye. We argue in (...) favor of the latter position, drawing on parallels from earlier debates around genetic exceptionalism in bioethics. We suggest there are risks to adopting a stance of “psychedelic ethical exceptionalism,” and propose that consistent ethical rules and evidentiary standards should be applied across all relevant areas of clinical medicine. Importantly, this does not preclude the possibility that changes to existing standards should be made; but if so, this should not be justified by appealing to the alleged uniqueness of psychedelics. (shrink)

Conley and colleagues (2023) explore how calls for broad public engagement (PE) in the case of heritable human genome editing are being put into action, reviewing the activities of five different i...

Precision medicine (PM) and genomics are increasingly scrutinized through the lens of health inequities. This is a welcome development for a field that, while concerned with health-related differen...

Retinoic acid (RA), a derivative of vitamin A, is essential for normal mammalian development. Developmental abnormalities induced by RA excess and vitamin A deficiency are different even though they affect the same organ systems, and it is clear that there are intraembryonic tissue differences in the requirement for RA. The developmental functions of RA are mediated by its effects on gene expression. In the nucleus, two different forms of RA bind to and activate two families of nuclear receptors, which themselves (...) co‐operate in initiating the transcription of target genes. In this article I propose that the amount of RA reaching the nucleus in different embryonic tissues is modulated by a mechanism involving three cytoplasmic binding proteins for retinol (CRBP I) and retinoic acid (CRABP I and II). Abnormalities of craniofacial development resulting from exposure of early neural plate stage embryos to RA excess have been studied in some detail; their initial stages involve alteration of both morphological development and the segment‐specific pattern of gene expression in the early hindbrain and its derived neural crest. This system is ideal for studying the relationships between retinoic acid receptors, retinoid binding proteins, and the development of genetic and morphological pattern. (shrink)

Kurt Gödel’s version of the Ontological Proof derives rather than assumes the crucial Possibility Claim: the claim that it is possible that something God-like exists. Gödel’s derivation starts off with a proof of the Possible Instantiation of the Positive: the principle that, if a property is positive, it is possible that there exists something that has that property. I argue that Gödel’s proof of this principle relies on some implausible axiological assumptions but it can be patched so that it only (...) relies on plausible principles. But Gödel’s derivation of the Possibility Claim also needs a substantial axiological assumption, which is still open to doubt. (shrink)

Are acids natural kinds? Or are they merely relevant kinds? Although acidity has been one of the oldest and most important concepts in chemistry, surprisingly little ink has been spilled on the natural kind question. I approach the question from the perspective of microstructural essentialism. After explaining why both Brønsted acids and Lewis acids are considered functional kinds, I address the challenges of multiple realization and multiple determination. Contra Manafu and Hendry, I argue that the stereotypical properties of acids are (...) not multiply realized. Instead, given the equivalence between the proton-donating and electron-accepting mechanisms of Brønsted and Lewis, respectively, I show that acidity as a property type can be identified with a unique microstructural property, namely the presence of a LUMO or other low energy empty orbital. In doing so, I defend the view that the Lewis theory encompasses Brønsted–Lowry, and that all Brønsted acids are also Lewis acids. Contra Hacking and Chang, I thus maintain that the different concepts of acidity do not crosscut, and that the hierarchy requirement is met. Finally, by characterizing natural kinds as powerful objects and by adopting a dispositional view of functions, I illustrate how the microessentialist can make sense of the latent and relational character of most acids. In sum, I contend that acids are genuine natural kinds, even for the microstructural essentialist. (shrink)

Acidity provides an interesting example of an everyday concept that developed fully into a scientific one; it is one of the oldest concepts in chemistry and remains an important one. However, up to now there has been no unity to it. Currently two standard theoretical definitions coexist ; the standard laboratory measure of acidity, namely the pH, only corresponds directly to the Br⊘nsted-Lowry concept. The lasting identity of the acidity concept in modern chemistry is based on the persistence of the (...) quotidian concept. This is suggestive for considerations of other scientific concepts. (shrink)

A large number of articles have been devoted to the application of “texture synthesis” for large regions and “inpainting” algorithms for small cracks in an image. A new approach that allows the simultaneous filling in of different structures and textures is discussed in this present study. The combination of structure inpainting and patch-based texture synthesis carried out for filling and updating the target region shows additional advantages over earlier approaches. The algorithm discussed here uses the patch-based inpainting with (...) isophote-driven patch-based texture synthesis at the core. In this algorithm, once the user selects the regions to be restored, the algorithm automatically searches and fills in these regions with the best matching information surrounding them. We have assigned high priorities to the pixels on the boundary and the structure by computing data terms D, and the texture and corners are prioritized by computing the confidence C of the pixel. We also regularized and weighted the confidence of the pixels, RC, to achieve a balance of the two. The patch search area near the pixel patch to be filled is bounded for algorithm speed improvement. Patch-based filling significantly improve execution speed compared with pixel-based filling. Filling in is done in such a way that the structure information arriving at the region boundaries is propagated inside. A number of examples on real and synthetic images are used to demonstrate the effectiveness of the algorithm. Robustness with respect to the shape of the selected target region is also demonstrated. (shrink)

Enzymes that degrade nucleic acids are emerging as important players in the pathogenesis of inflammatory disease. This is exemplified by the recent identification of four genes that cause the childhood inflammatory disorder, Aicardi‐Goutières syndrome (AGS). This is an autosomal recessive neurological condition whose clinical and immunological features parallel those of congenital viral infection. The four AGS genes encode two nucleases: TREX1 and the hetero‐trimeric Ribonuclease H2 (RNase H2) complex. The biochemical activity of these enzymes was initially characterised 30 years ago (...) but a role in neurological inflammation was entirely unanticipated until they were found to be mutated in AGS. This has led to a hypothesis that accumulation of intracellular nucleic acids occurs as a consequence of mutation in these enzymes and triggers an inflammatory response through activation of innate immune pattern recognition receptors. ©2007 Wiley Periodicals, Inc BioEssays 30:833–842, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

Ascorbic acid is a redox regulator in many physiological processes. Besides its antioxidant activity, many intriguing functions of ascorbic acid in the expression of immunoregulatory genes have been suggested. Ascorbic acid acts as a co‐factor for the Fe+2‐containing α‐ketoglutarate‐dependent Jumonji‐C domain‐containing histone demethylases (JHDM) and Ten eleven translocation (TET) methylcytosine dioxygenasemediated epigenetic modulation. By influencing JHDM and TET, ascorbic acid facilitates the differentiation of double negative (CD4−CD8−) T cells to double positive (CD4+CD8+) T cells and of T‐helper cells to different (...) effector subsets. Ascorbic acid modulates plasma cell differentiation and promotes early differentiation of hematopoietic stem cells (HSCs) to NK cells. These findings indicate that ascorbic acid plays a significant role in regulating both innate and adaptive immune cells, opening up new research areas in Immunonutrition. Being a water‐soluble vitamin and a safe micro‐nutrient, ascorbic acid can be used as an adjunct therapy for many disorders of the immune system. (shrink)

This article reports on a newly discovered bug in the original simulation argument. Two different ways of patching the argument are proposed, each of which preserves the original conclusion.

The "usual story" regarding molecular chemistry is that it is roughly an application of quantum mechanics. That is to say, quantum mechanics supplies everything necessary and sufficient, both ontologically and epistemologically, to reduce molecular chemistry to quantum mechanics. This is a reductive story, to be sure, but a key explanatory element of molecular chemistry, namely molecular structure, is absent from the quantum realm. On the other hand, typical characterizations of emergence, such as the unpredictability or inexplicability of molecular structure based (...) on quantum mechanics, do not characterize the relationship between molecular chemistry and quantum mechanics well either. A different scheme for characterizing reduction and emergence is proposed that accommodates the relationship between quantum mechanics and molecular chemistry and some initial objections to the scheme are considered. (shrink)

Many biologically active compounds including neurotransmitters, metabolic precursors, and certain drugs are accumulated intracellularly by transporters that are coupled to the transmembrane Na+ gradient. Amino acid neurotransmitter transporters play a key role in the regulation of extracellular amino acid concentrations and termination of neurotransmission in the CNSAbbreviations: CNS, central nervous system; GABA, γ‐aminobutyric acid; cDNA, complementary deoxyribonucleic acid; mRNA, messenger ribonucleic acid; NMDA, N‐methyl‐D‐aspartate; PKC, protein kinase C; PMA, phorbol 12‐myristate 13‐acetate; DAG, diacyl glycerol; R59022, DAG kinase inhibitor; AA, arachidonic (...) acid; ACHC, cis‐3‐aminocyclohexanecarboxylic acid; GAT‐A, ACHC‐sensitive GABA transporter; GAT‐B, β‐alanine‐sensitive GABA transporter; GLY‐1 and GLYT‐1, glycine transporters; PROT‐1, proline transporter; BGT‐1, betaine transporter.. Transporters for the major amino acid neurotransmitters glutamate, GABA, and glycine are found in both neurons and glial cells. Recent work has resulted in the identification of cDNAs encoding several amino acid neurotransmitter transport proteins, all of which belong to the Na+‐and Cl−‐dependent transporter gene family. The diversity of this family suggests a degree of transporter heterogeneity that is greater than that indicated by biochemical and pharmacological studies. (shrink)

The exploration of plant behavior on a cellular scale in a minimal invasive manner is key to understanding plant adaptations to their environment. Plant hormones regulate multiple aspects of growth and development and mediate environmental responses to ensure a successful life cycle. To monitor the dynamics of plant hormone actions in intact tissue, we need qualitative and quantitative tools with high temporal and spatial resolution. Here, we describe a set of biological instruments (reporters) for the analysis of the distribution and (...) signaling of various plant hormones. Furthermore, we provide examples of their utility for gaining novel insights into plant hormone action with a deeper focus on the drought hormone abscisic acid. (shrink)

Anthropological tests of patch choice models from optimal foraging theory have primarily employed acquisition rates as the currency of the model. Where foragers share their returns, acquisition rates may not be similar to consumption rates and thus may not be an appropriate currency to use when modeling foraging decisions. Indeed, on Ifaluk Atoll the distribution patterns of fish vary by fishing method and location. Previous analyses of Ifaluk patch choice decisions suggested that if Ifaluk fishers are trying to (...) maximize their production rates they should rarely torch fish for dogtoothed tuna. However, some men do spend considerable time and energy exploiting the dogtoothed tuna patch. To improve our understanding of the constraints and motivations influencing men’s decisions to exploit this patch, here I use per capita consumption rates as a currency, rather than production rates, to evaluate predictions generated from a patch choice model. Results indicate that although fish caught in other patches are more widely distributed than fish caught in the dogtoothed tuna patch, the consumption rates of torch fishers and their kin are still considerably lower than the consumption rates of men pursuing fish in other patches. Although these results are unable to explain why Ifaluk men exploit the dogtoothed tuna patch, an important explanatory hypothesis is eliminated. (shrink)

Henry Knowles Beecher, an icon of human research ethics, and Timothy Francis Leary, a guru of the counterculture, are bound together in history by the synthetic hallucinogen lysergic acid diethylamide. Beecher was a U.S. Army Lieutenant Colonel who received five battle stars, was inducted into the Legion of Merit, held the first endowed chair in his discipline, wrote at least three path-breaking papers, and is honored by two prestigious ethics awards in his name. Leary was a West Point dropout who (...) was obliged to leave a research assistant professorship, was convicted of violating the Marihuana Tax Act, was sentenced to 20 years in prison and broke out with the... (shrink)

The initial relationships between organisms leading to endosymbiosis and the first eukaryote are currently a topic of hot debate. Here, I present a theory that offers a gradual scenario in which the origins of phagocytosis and mitochondria are intertwined in such a way that the evolution of one would not be possible without the other. In this scenario, the premitochondrial bacterial symbiont became initially associated with a protophagocytic host on the basis of cooperation to kill prey with symbiont‐produced toxins and (...) reactive oxygen species (ROS). Subsequently, the cooperation was focused on the digestion stage, through the acidification of the protophagocytic cavities via exportation of protons produced by the aerobic respiration of the symbiont. The host gained an improved phagocytic capacity and the symbiont received organic compounds from prey. As the host gradually lost its membrane energetics to develop lysosomal digestion, respiration was centralized in the premitochondrial symbiont for energy production for the consortium. (shrink)

Acid attacks on women are increasing at alarming rates in Bangladesh, but the government has failed to provide medical care to the victims. Easily available sulfuric acid, which can mutilate a human face in moments, has emerged as a weapon used to disfigure a woman’s body. By the mid-1990s, activists had documented acid attacks, and urban protests were followed by demands for better medical care. I show how the interaction between local and international-level civil society organizations made international resources available (...) to local feminist groups engaged in domestic social struggles and helped to improve medical care for acid victims of Bangladesh. (shrink)

How vertebrates evolved different traits for acid excretion to maintain body fluid pH homeostasis is largely unknown. The evolution of Na+/H+ exchanger (NHE)‐mediated NH4+ excretion in fishes is reported, and the coevolution with increased ammoniagenesis and accompanying gluconeogenesis is speculated to benefit vertebrates in terms of both internal homeostasis and energy metabolism response to acidic stress. The findings provide new insights into our understanding of the possible adaptation of fishes to progressing global environmental acidification. In human kidney, titratable H+ (...) and NH4+ comprise the two main components of net acid excretion. V‐type H+‐ATPase‐mediated H+ excretion may have developed in stenohaline lampreys when they initially invaded freshwater from marine habitats, but this trait is lost in most fishes. Instead, increased reliance on NHE‐mediated NH4+ excretion is gradually developed and intensified during fish evolution. Further investigations on more species will be needed to support the hypothesis. Also see the video abstract here https://youtu.be/vZuObtfm-34. (shrink)

This paper uses scientific perspectivism as a lens for understanding acid experiments from the Chemical Revolution. I argue that this account has several advantages over several recent interpretations of this period, interpretations that do not neatly capture some of the historical experiments on acids. The perspectival view is distinctive in that it avoids discontinuity, allows for the rational resolution of disagreement, and is sensitive to the historical epistemic context.

Insulin is stored within the pancreas in an inactive Zn2+‐bound hexameric form prior to release. Similarly, clinical insulins contain Zn2+ and form multimeric complexes. Upon release from the pancreas or upon injection, insulin only becomes active once Zn2+ disengages from the complex. In plasma and other extracellular fluids, the majority of Zn2+ is bound to human serum albumin (HSA), which plays a vital role in controlling insulin pharmacodynamics by enabling removal of Zn2+. The Zn2+‐binding properties of HSA are attenuated by (...) non‐esterified fatty acids (NEFAs) also transported by HSA. Elevated NEFA concentrations are associated with obesity and type 2 diabetes. Here we present the hypothesis that higher NEFA levels in obese and/or diabetic individuals may contribute to insulin resistance and affect therapeutic insulin dose‐response profiles, through modulation of HSA/Zn2+ dynamics. We envisage this novel concept to have important implications for personalized treatments and management of diabetes‐related conditions in the future. (shrink)

Upon separation of the protein from the nucleic acid component of tobacco mosaic virus by phenol, using a fast and gentle procedure, the nucleic acid is infective in assays on tobacco leaves. A series of qualitative and quantitative control experiments demonstrates that the biological activity cannot depend on residual proteins in the preparation, but is a property of isolated nucleic acid which is thus the genetic material of the virus.

The acid rain issue came into prominence because scientists kept telling the world of acid rain's potential devastating effects. Yet, the acid rain debate was marked by mistrust between American and Canadian scientists. The signing of the Air Quality Accord in 1991 appears to have quelled this divisiveness and promises to bring about a new era of scientific cooperation. Using surveys of acid rain scientists in the United States and Canada across three time periods, this study finds both similarities and (...) differences between how Canadian and American scientists view many of the issues surrounding the acid rain debate. (shrink)

Although conservation attention has generally focused on large forest tracts, there is increasing evidence that smaller forest patches are important for both conservation and rural development. A study of forest patch conservation in a rural Costa Rican community found that, although forest patch conservation was influenced by landholding size, material factors did not account for all the variation in forest patches conservation behavior or conservation orientations of farmers. A qualitative interpretive approach, using semi-structured interviews, found that environmental values (...) were influenced by at least three factors. First, colonist farmers with direct experience with environmental degradation in other regions of Costa Rica were more likely to be concerned about environmental degradation. Second, childhood exposure to conservation played an important role in influencing conservation orientations. Third, the environment was frequently discussed in relation to the moral and social values present in religious doctrines. The study also found general support for forest conservation laws, and a clear indication that interest in forest conservation has grown in recent years. The study highlights the importance of environmental values, in conjunction with material factors, in influencing forest conservation in rural communities. (shrink)

Ideal families defined on a cardinalk often exhibit reflection properties. IfC ⫅k is a club, for example, thenC∩α is a club-in-α club-in-k often. In this paper we generalize this notion to ideal families defined on℘ kλ and exhibit some examples.

Tackling impaired bioenergetics in multiple sclerosis has been recently recognized as an innovative approach with therapeutic potential. Guanidinoacetic acid is an experimental nutrient that plays a significant role in high-energy phosphate metabolism. The preliminary trials suggest beneficial effects of supplemental GAA in MS, with GAA augments biomarkers of brain energy metabolism and improves patient-reported features of the disease. GAA can also impact other metabolic footprints of MS, including demyelination, oxidative stress, and GABA-glutamate imbalance. In this mini-review article, we summarize studies (...) evaluating GAA effectiveness in MS, explore mechanisms of GAA action, and discuss the challenges of using dietary GAA as an element of MS therapy. (shrink)

Nucleic acid hybridization is being increasingly used in viral diagnosis. Most of the assays described so far for this purpose require the use of radioactive probes. Their replacement by Non‐radioactive assays has many advantages and makes the technique feasible in routine diagnostic work. Non‐radioactive assays have had limited use but their diagnostic value has been demonstrated for a number of virus infections. They have the main advantages of employing stable probes, of avoiding safety hazards and of being easy and rapid (...) to perform with limited laboratory facilities. Their main disadvantage compared to radioactive assays is in having relatively low sensitivity. Improvements in probe construction, in labelling and detecting methods, in sample treatment and in hybridization conditions may well increase their usefulness. (shrink)

In vertebrate development, the HOX genes act to specify cell identity along much of the anterior‐posterior axis of the embryonic central nervous system. In all vertebrates examined to date, the vitamin A metabolite retinoic acid is implicated in the patterning of the anterior posterior axis and the induction of HOX gene expression. Two recent papers have extended the study of retinoic acid induction of HOX genes to the closest relatives of the vertebrates, amphioxus and tunicates(1,2). In both these species, exogenous (...) retinoic acid is able to induce ectopic expression of HOX 1 genes in the anterior central nervous system. This suggests that retinoic acid control of anterior‐posterior axis formation and HOX induction is not specific to vertebrates. However, in the more distantly related echinoderms and arthropods, retinoic acid does not seem to act in the same way. Thus the role of retinoic acid in anterior‐posterior axis specification may be a chordate innovation, perhaps linked to the evolution of another chordate character, the dorsal neural tube. (shrink)

The study of haemopoiesis enables us to address one of the central questions of developmental biology, concerning the molecular mechanisms by which a multipotent cell develops into distinct differentiated progeny. Recent work(1) suggests specific roles for retinoic acid receptors at two distinct stages of haemopoiesis. Continuous cell lines of lymphohaemopoietic progenitors were established by infection with a retrovirus containing a dominant negative retinoic acid receptor. The cell lines depend on stem cell factor for their proliferation and can be induced to (...) diffentiate into B‐lymphocytes, erythrocytes, neutrophils, monocytes, mast cells and megakaryocytes. Since lymphohaemopoietic progenitors represent less than 0.01% of nucleated marrow cells, immortalised progenitors provide a valuable system with which to study haemopoiesis on a molecular level. (shrink)