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 present study examines the physiological alterations in prolactin (PRL) messenger ribonucleic acid (mRNA) and serum PRL levels during the rat estrous cycle and the effed of naloxone, an endogenous opioid peptide receptor antagonist, on PRL gene expression during the rat estrous cycle. Adult female rats exhibiting at least two consecutive 4-day estrous cycles were used in this study. A single injection of naloxone (2mg/kg b.w.) or saline was given sc 30 mm prior to decapitation. Animals were sacrificed (...) at 10:00 h of each stage of the estrous cycle, and at 2-h intervals from 10:00 h to 20:00 h during the proestrus. PRL mRNA and serum PRL levels were determined by an RNA-blot hybridization with the rat PRL cDNA probe and by a PRL radioimmunoassay, respectively. PRL mRNA and serum PRL levels were not dramatically altered in the morning of each stage of diestrus I, II, and proestrus, and naloxone failed to modify the two parameters. During estrus naloxone clearly suppressed serum PRL levels, but it was unable to modify PRL mRNA levels. A more detailed examination of the proestrus stage revealed that PRL mRNA and serum PRL levels fluctuated as a function of time: PRL mRNA levels reached a maximum level at 12:00 h and gradually decreased until 18:00 h. PRL mRNA levels then rose at 20:00 h. No difference in PRL mRNA levels between the control and naloxone-treated groups was observed. Changes in serum PRL level during proestrus were conversely related to changes in PRL mRNA: serum PRL levels were low from 10:00 h to 14:00 h, then increased and reached a maximum level at 16:00-18:00 h. Following then, serum PRL levels were decreased. Naloxone was effective in suppressing the characteristic afternoon surge of PRL from 16:00 h to 20:00 h. These data clearly showed that alterations in PRL mRNA levels were conversely correlated with changes in serum PRL levels on proestrus, indicating differential regulation of PRL gene expression and secretion. (shrink)

Within the sedimentation diagram of infective RNA preparations isolated from Tobacco Mosaic Virus, undegraded molecules form a sharp peak with a molecular weight corresponding to the total RNA content of the virus particle. Degradation kinetics by ribonuclease is of the linear, single-target type, indicating that the RNA is single-stranded. The intact RNA of a virus particle thus forms one big single-stranded molecule. Quantitative evaluation of the effect degradation by RNA-ase on the infectivity of the RNA shows that the integrity of (...) the entire molecule is required for its biological activity. (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)

Life on earth is bound together by a common heritage, centered around a molecule that is present in almost every living cell of every living creature. Deoxyribonucleic acid (DNA), composed of four base pairs, the nucleic acids thymine, adenine, cytosine, and guanine, encodes the data that directs, in conjunction with the environment, the development and metabolism of all nondependent living creatures. Except for some viruses that rely only on ribonucleic acid (RNA), all living things are built by (...) the interaction of DNA and RNA within cells and their environments. There is no worldwide consensus yet as to whether portions of the human genome should be granted intellectual property protection, as indeed they are in the United States and a number of other nations. DNA posed numerous challenges to the legal framework for patent protection and may suggest developing an entirely new social and legal category recognizing its uniqueness. (shrink)

The universally recognized backbone of molecular biology describes the flow of genetic information from deoxyribonucleic acid (DNA) to ribonucleic acid (RNA) to protein or gene product, that is, DNA is transcribed into another nucleic acid (RNA), which is single stranded, next some types of RNA are in turn translated into proteins. Translation of nucleic acids to proteins is literally a translation from the genomic language to the metabolic language. Codons formed of a sequence of three nucleic (...) acids summon a specific amino acid. Translation from codons to proteins, that is, protein synthesis, takes place by specialized machinery comprising mRNA, ribosomes, and free amino acids. Inferring the structure of DNA opened the door for tremendous advances in understanding the role of genes in creating life, directing replication, and ongoing metabolic processes responsible for maintaining life at both the cellular and organism level. (shrink)

In organisms, ribonucleic acid plays an essential role. Its function is being discovered more and more. Due to the conserved nature of RNA sequences, its function mainly depends on the RNA secondary structure. The discovery of an approximate relationship between two RNA secondary structures helps to understand their functional relationship better. It is an important and urgent task to explore structural similarities from the graphical representation of RNA secondary structures. In this paper, a novel graphical analysis method based (...) on the triple vector curve representation of RNA secondary structures is proposed. A combinational method involving a discrete wavelet transform and fractal dimension with sliding window is introduced to analyze and compare the graphs derived from feature extraction; after that, the distance matrix is generated. Then, the distance matrix is analyzed by clustering and visualized as a clustering tree. RNA virus and noncoding RNA datasets are applied to perform experiments and analyze the clustering tree. The results show that the proposed method yields more accurate results in the comparison of RNA secondary structures. (shrink)

In the last 10 years, we have witnessed a blooming of targeted genome editing systems and applications. The area was revolutionized by the discovery and characterization of the transcription activator‐like effector proteins, which are easier to engineer to target new DNA sequences than the previously available DNA binding templates, zinc fingers and meganucleases. Recently, the area experimented a quantum leap because of the introduction of the clustered regularly interspaced short palindromic repeats (CRISPR)‐associated protein (Cas) system (clustered regularly interspaced short palindromic (...) sequence). This ribonucleoprotein complex protects bacteria from invading DNAs, and it was adapted to be used in genome editing. The CRISPR ribonucleic acid (RNA) molecule guides to the specific DNA site the Cas9 nuclease to cleave the DNA target. Two years and more than 1000 publications later, the CRISPR‐Cas system has become the main tool for genome editing in many laboratories. Currently the targeted genome editing technology has been used in many fields and may be a possible approach for human gene therapy. Furthermore, it can also be used to modifying the genomes of model organisms for studying human pathways or to improve key organisms for biotechnological applications, such as plants, livestock genome as well as yeasts and bacterial strains. (shrink)

RNA can catalyse chemical reactions through its ability to fold into complex three‐dimensional structures and to specifically bind small molecules and divalent metal ions. The 2′‐hydroxyl groups of the ribose moieties contribute to this exceptional reactivity of RNA, compared to DNA. RNA is not only able to catalyse phosphate ester transfer reactions in ribonucleic acids, but can also show aminoacyl esterase activity, and is probably able to promote peptide bond formation. Bearing its potential for functioning both as a genome (...) and as a gene product, RNA is suitable for in vitro evolution experiments enabling the selection of molecules with new properties. The growing repertoire of RNA catalysed reactions will establish RNA as a primordial molecule in the evolution of life. (shrink)

The fate of eukaryotic proteins, from their synthesis to destruction, is supervised by the ubiquitin–proteasome system (UPS). The UPS is the primary pathway responsible for selective proteolysis of intracellular proteins, which is guided by covalent attachment of ubiquitin to target proteins by E1 (activating), E2 (conjugating), and E3 (ligating) enzymes in a process known as ubiquitylation. The UPS can also regulate protein synthesis by influencing multiple steps of RNA (ribonucleic acid) metabolism. Here, recent publications concerning the interplay between (...) the UPS and different types of RNA are reviewed. This interplay mainly involves specific RNA‐binding E3 ligases that link RNA‐dependent processes with protein ubiquitylation. The emerging understanding of their modes of RNA binding, their RNA targets, and their molecular and cellular functions are primarily focused on. It is discussed how the UPS adapted to interact with different types of RNA and how RNA molecules influence the ubiquitin signaling components. (shrink)

Abstract.Arthur Peacocke was one of the most important scholars to contribute to the modern dialogue on science and religion, and for this he is remembered in the science‐religion community. Many people, however, are unaware of his exceptional career as a biochemist prior to his decision to pursue a life working as a clergyman in the Church of England. His contributions to studies of deoxyribonucleic acid (DNA) structure, effects of radiation damage on DNA, and on the interactions of DNA and (...) proteins are among the most important in the field at the time and have had a lasting scientific impact that is still felt today. Peacocke's arguments with Jacques Monod over stochastic (chance) and deterministic (necessity) processes driving evolution became important independently for both the science and the religion communities and appear to have contributed significantly to his decision to become involved in science‐religion dialogue rather than continuing his work exclusively in the field of science. Nevertheless, although Peacocke took on an active church life and ceased his experimental work, he never left science but continued to read the scientific literature and published a scientific review on different approaches in defining DNA structure as recently as 2005. (shrink)

Open theism denies that God has definite exhaustive foreknowledge, and affirms that God takes certain risks when creating the universe. Critics of open theism often complain that the risks are too high. Perhaps there is something morally wrong with God taking a risk in creating a universe with an open future. Open theists have tried to respond by clarifying how much risk is involved in God creating an open universe, though we argue that it remains unclear how much risk is (...) actually involved. We claim that open theists need to start developing theories about how God manages risks in order to bring about His purposes for the universe. In this article, we will take a philosophical and biological perspective on risk management that adds plausibility to open theism. We will consider how God can use different risk‐management, surveillance, and redundancy systems in the natural world in order to accomplish His goals. (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)

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)

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)

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)

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)

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)

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)

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)

For a period of several years the philosopher of science Hasok Chang has promoted various inter-related views including pluralism, pragmatism, and an associated view of natural kinds. He has also argued for what he calls the persistence of everyday terms in the scientific view. Chang claims that terms like phlogiston were never truly abandoned but became transformed into different concepts that remain useful. On the other hand, Chang argues that some scientific terms such as acidity have suffered a form of (...) “rupture”, especially in the case of the modern Lewis definition of acids. Chang also complains that the degree of acidity of a Lewis acid cannot be measured using a pH meter and seems to regard this as a serious problem. The present paper examines some of these views, especially what Chang claims to be a rupture in the definition of acidity. It is suggested that there has been no such rupture but a genuine generalization, on moving from the Brønsted-Lowry theory to the Lewis theory of acidity. It will be shown how the quantification and measurement of Lewis acidity can easily be realized through the use of equilibrium theory and the use of stability constants. (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.

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)

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)

Among the many vivid metaphors in Darwin’s Dangerous Idea, one stands out. The understanding of how cumulative natural selection gives rise to adaptations is, Dennett says, like a “universal acid”—an idea so powerful and corrosive of conventional wisdom that it dissolves all attempts to contain it within biology. Like most good ideas, this one is very simple: Once replicators (material objects that are faithfully copied) come to exist, some will replicate more rapidly than others, leading to adaptation by natural (...) selection. The great power of the idea is that the resulting adaptations can be understood by asking what leads to efficient, rapid replication. Given that ideas seem to replicate, it is natural that Dawkins (1976, 1982), Dennett (1992), and others have explored the possibility of using this idea to explain cultural evolution. (shrink)

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)

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)

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)

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)

Among the many vivid metaphors in Darwin’s Dangerous Idea, one stands out. The understanding of how cumulative natural selection gives rise to adaptations is, Dennett says, like a “universal acid”—an idea so powerful and corrosive of conventional wisdom that it dissolves all attempts to contain it within biology. Like most good ideas, this one is very simple: Once replicators (material objects that are faithfully copied) come to exist, some will replicate more rapidly than others, leading to adaptation by natural (...) selection. The great power of the idea is that the resulting adaptations can be understood by asking what leads to efficient, rapid replication. Given that ideas seem to replicate, it is natural that Dawkins (1976, 1982), Dennett (1992), and others have explored the possibility of using this idea to explain cultural evolution. (shrink)

We consider the evidence that RA†, the vitamin A metabolite, is involved in three fundamental aspects of the development of the CNS: (1) the stimulation of axon outgrowth in particular neuronal sub‐types; (2) the migration of the neural crest; and (3) the specification of rostrocaudal position in the developing CNS (forebrain, midbrain, hindbrain, spinal cord). The evidence we discuss involves RA‐induction of neurites in cell cultures and explants of neural tissue; the teratological effects of RA on the embryo's nervous system; (...) the observation that RA can be detected endogenously in the spinal cord; and the fact that the receptors and binding proteins for RA are expressed in precise domains and neuronal cell types within the nervous system. (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)

A fast growing family of ATPases has recently been highlighted. It was named the AAA family, for ATPases Associated to a variety of cellular Activities. The key feature of the family is a highly conserved module of 230 amino acids present in one or two copies in each protein. Despite extensive sequence conservation, the members of the family fulfil a large diversity of cellular functions: cell cycle regulation, gene expression in yeast and HIV, vesicle‐mediated transport, peroxisome assembly, 26S protease function (...) etc. In addition, several members of this family can be found in the same organism (up to 17 in S. cerevisiae). The contrast between functional diversity and structural conservation of the module, from archaebacteria to mammals, suggests that it plays an essential, but as yet unknown, role at key points of the cellular machinery. Two (non‐exclusive) such possibilities are: (1) ATP‐dependent proteasome function and (2) ATP‐dependent anchorage of proteins. Finally, the basic biochemical activity of the AAA module is still a matter of speculation, and we propose that it acts as an ATP‐dependent protein clamp. (shrink)

The central dogma of molecular biology dictates that, with only a few exceptions, information proceeds from DNA to protein through an RNA intermediate. Examining the enigmatic steps from prebiotic to biological chemistry, we take another road suggesting that primordial peptides acted as template for the self-assembly of the first nucleic acids polymers. Arguing in favour of a sort of archaic “reverse translation” from proteins to RNA, our basic premise is a Hadean Earth where key biomolecules such as amino acids, polypeptides, (...) purines, pyrimidines, nucleosides and nucleotides were available under different prebiotically plausible conditions, including meteorites delivery, shallow ponds and hydrothermal vents scenarios. Supporting a protein-first scenario alternative to the RNA world hypothesis, we propose the primeval occurrence of short two-dimensional peptides termed “selective amino acid- and nucleotide-matching oligopeptides” (henceforward SANMAOs) that noncovalently bind at the same time the polymerized amino acids and the single nucleotides dispersed in the prebiotic milieu. In this theoretical paper, we describe the chemical features of this hypothetical oligopeptide, its biological plausibility and its virtues from an evolutionary perspective. We provide a theoretical example of SANMAO’s selective pairing between amino acids and nucleosides, simulating a poly-Glycine peptide that acts as a template to build a purinic chain corresponding to the glycine’s extant triplet codon GGG. Further, we discuss how SANMAO might have endorsed the formation of low-fidelity RNA’s polymerized strains, well before the appearance of the accurate genetic material’s transmission ensured by the current translation apparatus. (shrink)

In January 2014, a letter and original research article were published in Nature describing a process whereby somatic mouse cells could be converted into stem cells by subjecting them to stress. These “stimulus-triggered acquisition of pluripotency” cells were shown to be capable of contributing to all cell types of a developing embryo, and extra-embryonic tissues. The lead author of the publications, Haruko Obokata, became an overnight celebrity in Japan, where she was dubbed the new face of Japanese science. However, in (...) the weeks that followed publication of the research, issues arose. Other laboratories and researchers found that they were unable to replicate Obokata et al.’s work. Closer scrutiny of the papers by the scientific community also suggested that there was manipulation of images that had been published, and Obokata was accused of misconduct. Those who should have been supervising her work were also heavily criticised. The STAP cell saga of 2014 is used as an example to highlight the importance of trust and replication in twenty-first century biological science. The role of trust in the scientific community is highlighted, and the effects on interactions between science and the public examined. Similarly, this essay aims to highlight the importance of replication, and how this is understood by researchers, the media, and the public. The expected behaviour of scientists in the twenty-first century is now more closely scrutinised. (shrink)

Wana Manitpisitkul1, Sabrina Lee2, Matthew Cooper31Department of Pharmacy, University of Maryland Medical Center, Baltimore, MD, USA; 2Solid Organ Transplant Program, University of Utah Health Care, Salt Lake City, UT, USA; 3Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA: Addition of mycophenolate mofetil to calcineurin-based immunosuppressive therapy has led to a significant improvement in graft survival and reduction of acute rejection in renal transplant recipients. However, in clinical practice, MMF dose reduction, interruption, or discontinuation due to hematological (...) and gastrointestinal side-effects occurred in up to 50% of the patients. Large retrospective analyses have demonstrated that patients requiring MMF dose manipulation due to adverse events experienced a higher rate of rejection and graft loss. Enteric-coated mycophenolate sodium was developed with the goal of improving upper GI side-effects. Here, we review the efficacy and safety of EC-MPS in de novo kidney transplant recipient, and in stable renal transplant patients who were converted from MMF. The changes in GI-related adverse events using patient-reported outcome instruments are also reviewed.Keywords: enteric-coated mycophenolate sodium, mycophenolate mofetil, kidney transplant, efficacy, gastrointestinal tolerability. (shrink)

Extracellular nucleic acids are found in different biological fluids in the organism and in the environment: DNA is a ubiquitous component of the organic matter pool in the soil and in all marine and freshwater habitats. Data from recent studies strongly suggest that extracellular DNA and RNA play important biological roles in microbial communities and in higher organisms. DNA is an important component of bacterial biofilms and is involved in horizontal gene transfer. In recent years, the circulating extracellular nucleic acids (...) were shown to be associated with some diseases. Attempts are being made to develop noninvasive methods of early tumor diagnostics based on analysis of circulating DNA and RNA. Recent observations demonstrated the possibility of nucleic acids exchange between eukaryotic cells and extracellular space suggesting their participation in so far unidentified biological processes. BioEssays 29:654–667, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

Fatty acids (FAs) are well known to serve as substrates for reactions that provide cells with membranes and energy. In contrast to these metabolic reactions, the physiological importance of FAs themselves known as free FAs (FFAs) in cells remains obscure. Since accumulation of FFAs in cells is toxic, cells must develop mechanisms to detoxify FFAs. One such mechanism is to sequester free polyunsaturated FAs (PUFAs) into a droplet‐like structure assembled by Fas‐Associated Factor 1 (FAF1), a cytosolic protein. This sequestration limits (...) access of PUFAs to Fe2+, thereby preventing Fe2+‐catalyzed PUFA peroxidation. Consequently, assembly of the FAF1‐FFA complex is critical to protect cells from ferroptosis, a cell death pathway triggered by PUFA peroxidation. The observations that free PUFAs in cytosol are not randomly diffused but rather sequestered into a membraneless complex should open new directions to explore signaling pathways by which FFAs regulate cellular physiology. (shrink)

This essay responds to Hirstein, Sifferd and Fagan’s book, Responsible Brains, which claims that executive function is the guiding mechanism that supports both responsible agency and the necessity for some excuses. In contrast, I suggest that executive function is not the universal acid and the neuroscience at present contributes almost nothing to the necessary psychological level of explanation and analysis. To the extent neuroscience can be useful, it is virtually entirely dependent on well-validated psychology to correlate with the neuroscientific (...) variables under investigation. The essay considers what executive function is and what the neuroscience adds to our understanding of it. Then it addresses moral and legal responsibility generally, and specific doctrines. Executive function is seldom found to be the most perspicuous approach to any of the general or specific moral and legal questions. (shrink)