Whatever happened to SRY?

The mammalian sex-determining gene, SRY, was identified by positional cloning approximately 10 years ago. Since its discovery, intense research into this gene has been directed on two main fronts: elucidation of its function in development of the testis and examination of its singular evolutionary history. The role or SRY as the testis-determining factor (TDF) places it at a crucial point in the highly conserved morphogenetic process of vertebrate gonadogenesis. None of the genes that directly activate SRY nor any of its immediate downstream targets have yet been positively identified. Several genes, however, such as SF1, DAX1, and SOX9, whose spatial and temporal expression profiles overlap with that of SRY, are strongly implicated as co-regulators of gonadogenesis. Molecular genetic manipulation of these genes in mice has shown that they are indispensable to sexual development. Remarkably, its key position in this cascade of gene action has not protected SRY from strong yet poorly understood selective forces that have caused it to evolve rapidly in mammals. The evolution of SRY has been characterized not only by rapid sequence divergence within mammals, but also by structural changes such as intron insertion, gene amplification, and deletion.     

Resistance to β-lactam antibiotics

-lactams have a long history in the treatment of infectious diseases, though their use has been and continues to be confounded by the development of resistance in target organisms. -lactamases, particularly in Gram-negative pathogens, are a major determinant of this resistance, although alterations in the -lactam targets, the penicillin-binding proteins (PBPs), are also important, especially in Gram-positive pathogens. Mechanisms for the efflux and/or exclusion of these agents also contribute, though often in conjunction these other two. Approaches for overcoming these resistance mechanisms include the development of novel -lactamase-stable -lactams, -lactamase inhibitors to be employed with existing -lactams, -lactam compounds that bind strongly to low-affinity PBPs and agents that potentiate the activity of existing -lactams against low-affinity PBP-producing organisms.Received 9 February 2004; received after revision 30 March 2004; accepted 19 April 2004     

Conversion of 17α-hydroxypregnenolone to cortisol

Zusammenfassung Nebennierenschnitte von Ratten, Meerschweinchen und Menschen synthetisierten 17-Hydroxyprogesteron, 11-Deoxycortisol und Cortisol aus 17-Hydroxypregnenolon. Diese Verbindung, als Ausgangsprodukt für die Cortisolsynthese, ist ebenso wirksam wie pregnenolon. Die Umwandlung von 17-Hydroxypregnenolon in Dehydroepiandrosteron verläuft weniger vollkommen als zu 17-Hydroxycorticoiden.     

Poincaré's Contributions to Relativistic Dynamics

In this paper I concentrate on the dynamic aspects of the special theory of relativity (in the non-Minkowski formalism), and not on the kinematic part of the story as is usually done. Following up the dynamic story leads to a new point of view as to Poincaré's important role in the development of special relativity. Much of Poincaré's dynamic work did not enter into Einstein's 1905 theory, since Einstein was mainly occupied with kinematics. However, the dynamic part is most fundamental in the development of the special theory of relativity after 1905. In this paper I consider the main developments of relativistic dynamics in which I demonstrate that much response to Poincaré's dynamic research can be found. I argue that Poincaré's dynamic work assisted in departing from Einstein's electrodynamic theory towards relativistic dynamics (independent of electrodynamics).     

Protein folding and degradation in bacteria: to degrade or not to degrade? That is the question

In Escherichia coli protein quality control is carried out by a protein network, comprising chaperones and proteases. Central to this network are two protein families, the AAA+ and the Hsp70 family. The major Hsp70 chaperone, DnaK, efficiently prevents protein aggregation and supports the refolding of damaged proteins. In a special case, DnaK, together with the assistance of the AAA+ protein ClpB, can also refold aggregated proteins. Other Hsp70 systems have more specialized functions in the cell, for instance HscA appears to be involved in the assembly of Fe/S proteins. In contrast to ClpB, many AAA+ proteins associate with a peptidase to form proteolytic machines which remove irreversibly damaged proteins from the cellular pool. The AAA+ component of these proteolytic machines drives protein degradation. They are required not only for recognition of the substrate but also for substrate unfolding and translocation into the proteolytic chamber. In many cases, specific adaptor proteins modify the substrate binding properties of AAA+ proteins. While chaperones and proteases do not appear to directly cooperate with each other, both systems appear to be necessary for proper functioning of the cell and can, at least in part, substitute for one another. RID="*" ID="*"Corresponding author.     

Are plants cognitive? A reply to Adams

According to F. Adams [this journal, vol. 68, 2018] cognition cannot be realized in plants or bacteria. In his view, plants and bacteria respond to the here-and-now in a hardwired, inflexible manner, and are therefore incapable of cognitive activity. This article takes issue with the pursuit of plant cognition from the perspective of an empirically informed philosophy of plant neurobiology. As we argue, empirical evidence shows, contra Adams, that plant behavior is in many ways analogous to animal behavior. This renders plants suitable to be described as cognitive agents in a non-metaphorical way. Sections two to four review the arguments offered by Adams in light of scientific evidence on plant adaptive behavior, decision-making, anticipation, as well as learning and memory. Section five introduces the ‘phyto-nervous’ system of plants. To conclude, section six resituates the quest for plant cognition into a broader approach in cognitive science, as represented by enactive and ecological schools of thought. Overall, we aim to motivate the idea that plants may be considered genuine cognitive agents. Our hope is to help propel public awareness and discussion of plant intelligence once appropriately stripped of anthropocentric preconceptions of the sort that Adams' position appears to exemplify.     

Why isPyrrhocoris apterus insensitive to precocene II?

Summary Precocene II (P II) was applied to the adult females of 2 Pyrrhocorid bugs —Pyrrhocoris apterus (insensitive to P II) andDysdercus cingulatus (sensitive to P II)-subjected to allatectomy and intraspecific or interspecific reimplantations of corpus allatum (CA). The failure of P II to inhibit ovarian development inP. apterus appears to be caused by both a low sensitivity to P II of the CA itself and unknown anti-precocene mechanisms outside the CA.Precocene II was kindly supplied by Zoecon.     

Do we need pharmacogenetics to personalize antidepressant therapy?

This review examines the role of drug metabolism and drug target polymorphism in determining the clinical response to antidepressants. Even though antidepressants are the most effective available treatment for depressive disorders, there is still substantial need for improvement due to the slow onset of appreciable clinical improvement and the association with side effects. Moreover, a substantial group of patients receiving antidepressant therapy does not achieve remission or fails to respond entirely. Even if the large variation in antidepressant treatment outcome across individuals remains poorly understood, one possible source of this variation in treatment outcome are genetic differences. The review focuses on a few polymorphisms which have been extensively studied, while reporting a more comprehensive reference to the existing literature in table format. It is relatively easy to predict the effect of polymorphisms in drug metabolizing enzymes, such as cytochromes P450 2D6 (CYP2D6) and cytochrome P450 2C19 (CYP2C19), which may be determined in the clinical context in order to explain or prevent serious adverse effects. The role of target polymorphism, however, is much more difficult to establish and may be more relevant for disease susceptibility and presentation rather than for response to therapy.     

A researcher’s guide to the galaxy of IRESs

The idea of internal initiation is frequently exploited to explain the peculiar translation properties or unusual features of some eukaryotic mRNAs. In this review, we summarize the methods and arguments most commonly used to address cases of translation governed by internal ribosome entry sites (IRESs). Frequent mistakes are revealed. We explain why “cap-independent” does not readily mean “IRES-dependent” and why the presence of a long and highly structured 5′ untranslated region (5′UTR) or translation under stress conditions cannot be regarded as an argument for appealing to internal initiation. We carefully describe the known pitfalls and limitations of the bicistronic assay and artefacts of some commercially available in vitro translation systems. We explain why plasmid DNA transfection should not be used in IRES studies and which control experiments are unavoidable if someone decides to use it anyway. Finally, we propose a workflow for the validation of IRES activity, including fast and simple experiments based on a single genetic construct with a sequence of interest.     

Do Media Data Help to Predict German Industrial Production?

In an uncertain world, decisions by market participants are based on expectations. Therefore, sentiment indicators reflecting expectations have a proven track record at predicting economic variables. However, survey respondents largely perceive the world through media reports. Here, we want to make use of that. We employ a rich dataset provided by Media Tenor International, based on sentiment analysis of opinion‐leading media in Germany from 2001 to 2014, transformed into several monthly indices. German industrial production is predicted in a real‐time out‐of‐sample forecasting experiment and media indices are compared to a huge set of alternative indicators. Media data turn out to be valuable for 10‐ to 12‐month horizon forecasts, which is in line with the lag between monetary policy announcements and their effect on industrial production. This holds in the period during and after the Great Recession when many models fail. Copyright © 2016 John Wiley & Sons, Ltd.     

From classical to Voigt’s molecular models in elasticity

In the first decades of the nineteenth century the French mechanicians—Cauchy and Poisson amongst them—developed a theory of linear elasticity according to which matter is composed of material points. They believed that these points interact by means of opposite central forces, whose magnitude depends on the length of the segment joining the particles. This theory suggested that homogeneous isotropic materials were characterized by a unique elastic constant. Later experiments, however, showed that two elastic constants were necessary. These results undermined the corpuscular model of matter as well as the interpretation of elasticity in terms of central intermolecular actions. The continuous theory of Green, based on the postulate that a potential function exists, gained fresh consensus in light of these experiments. These opposite views continued throughout the nineteenth century until Woldemar Voigt proposed a molecular model confirmed by experiments. This article presents the theories of each of these scientists and describes the contrasting views of nineteenth-century mechanicians.     

Structural and dynamical features contributing to thermostability in α-amylases

In recent years an increasing number of studies on thermophilic and hyperthermophilic proteins aiming to elucidate determinants of protein thermostability have yielded valuable insights about the relevant mechanisms. In particular, comparison of homologous enzymes with different thermostabilities (isolated from psychrophilic, mesophilic, thermophilic and hyperthermophilic organsims) offers a unique opportunity to determine the strategies of thermal adaptation. In this respect, the medium-sized amylolytic enzyme α-amylase is a well-established representative. Various studies on α-amylases with very different thermostabilities (melting temperature T_m = 40–110°C) report structural and dynamical features as well as thermodynamical properties which are supposed to play key roles in thermal adaptation. Here, results from selected homologous α-amylases are presented and discussed with respect to some new and recently proposed strategies to achieve thermostability.Received 28 February 2005; received after revision 29 April 2005; accepted 19 May 2005     

Conversion ofβ-mercaptopyruvate to 2-mercaptoethanol by yeast enzymes

Zusammenfassung Hefeextrakt decarboxyliert-Mercaptobrenztraubensäure zu 2-Mercaptoazetaldehyd, welches von DPNH und Alkohol-Dehydrogenase zu 2-Mercaptoethanol reduziert wird. Enzymatische und chemische Messungen bestätigen den Reaktionsmechanismus.

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Supported by grants of the USPH, C-4681 and C-3211, and by a grant of the American Heart Association Inc., New York.     

Cholinesterase reactivators — Contribution to the study of their metabolic effects

Summary Cholinesterase reactivators — trimedoxim, methoxim and obidoxim — injected in the dose of 20 mg/kg s.c., increase muscle glycogen concentration in normal, but not in adrenalectomized rats. This effect may be in connection with simoultaneously found rise of serum corticosteron level. Trimedoxim decreases adrenaline, methoxim and obidoxim noradrenaline concentration in adrenals.