From Beads on a String to the Pearls of Regulation: the Structure and Dynamics of Chromatin

The assembly of eukaryotic chromatin, and the bearing of its structural organization on the regulation of gene expression, were the central topics of a recent conference organized jointly by the Biochemical Society and Wellcome Trust. A range of talks and poster presentations covered topical aspects of this research field and illuminated recent advances in our understanding of the structure and function of chromatin. The two-day meeting had stimulating presentations complemented with lively discourse and interactions of participants. In the present paper, we summarize the topics presented at the meeting, in particular highlighting subjects that are reviewed in more detail within this issue of Biochemical Society Transactions. The reports bring to life the truly fascinating molecular and structural biology of chromatin

Through Ancient Rings Thread Programming Strings

A new crystal structure of assembled subunits from the eukaryotic exosome complex gives insight into the interactions underpinning its various functions (Bonneau et al., 2009). Here, we focus on what the emerging structures tell us about the regulation of the exosome interactions with, and actions on, RNA

Increased adrenal steroid secretion in response to CRF in women with hypothalamic amenorrhea

Objectie: To evaluate adrenal steroid hormone secretion in response to corticotropin-releasing factor (CRF) or to adrenocorticotropin hormone in women with hypothalamic amenorrhea. Design: Controlled clinical study. Setting: Department of Reproductive Medicine and Child Development, Section of Gynecology and Obstetrics, University of Pisa, Italy. Patient(s): Fifteen women with hypothalamic amenorrhea were enrolled in the study. Eight normal cycling women were used as control group. Interention(s): Blood samples were collected before and after an injection of ovine CRF (0.1 g/kg iv bolus) or after synthetic ACTH (0.25 mg iv). Main outcome measure(s): Plasma levels of ACTH, 17-hydroxypregnenolone (17OHPe), progesterone (P), dehydroepiandrosterone (DHEA), 17-hydroxyprogesterone (17OHP), cortisol (F), 11-deoxycortisol (S) and androstenedione (A). Result(s): Basal plasma concentrations of ACTH, cortisol, 11-deoxycortisol, DHEA and 17OHPe were significantly higher in patients than in controls, whereas plasma levels of progesterone and 17-OHP were significantly lower in patients than in controls. In amenorrheic women the ratio of 17-OHPe/DHEA, of 17-OHPe/17-OHP and of 11-deoxycortisol/cortisol were significantly higher than in controls, while a significant reduction in the ratio of 17-OHP/androstenedione, of 17-OHP/11-deoxycortisol was obtained. In response to corticotropin-releasing factor test, plasma levels of ACTH, cortisol, 17-OHP, 11-deoxycortisol, DHEA and androstenedione were significantly lower in patients than in controls. In response to adrenocorticotropin hormone, plasma levels of 17-OHP, androstenedione and androstenedione/cortisol were significantly higher in patients than in controls. Conclusions: Patients suffering for hypothalamic amenorrhea showed an increased activation of hypothalamus-pituitaryadrenal (HPA) axis, as shown by the higher basal levels and by augmented adrenal hormone response to corticotropin-releasing factor administration. These data suggest a possible derangement of adrenal androgen enzymatic pathway

Thoracic involvement in generalised lymphatic anomaly (or lymphangiomatosis)

Generalised lymphatic anomaly (GLA), also known as lymphangiomatosis, is a rare disease caused by congenital abnormalities of lymphatic development. It usually presents in childhood but can also be diagnosed in adults. GLA encompasses a wide spectrum of clinical manifestations ranging from singleorgan involvement to generalised disease. Given the rarity of the disease, most of the information regarding it comes from case reports. To date, no clinical trials concerning treatment are available. This review focuses on thoracic GLA and summarises possible diagnostic and therapeutic approaches

Structure and mechanism of bacterial tripartite efflux pumps.

Efflux pumps are membrane proteins which contribute to multi-drug resistance. In Gram-negative bacteria, some of these pumps form complex tripartite assemblies in association with an outer membrane channel and a periplasmic membrane fusion protein. These tripartite machineries span both membranes and the periplasmic space, and they extrude from the bacterium chemically diverse toxic substrates. In this chapter, we summarise current understanding of the structural architecture, functionality, and regulation of tripartite multi-drug efflux assemblies.ER

Stochastic simulations of minimal cells: the Ribocell model

<p>Abstract</p> <p>Background</p> <p>Over the last two decades, lipid compartments (liposomes, lipid-coated droplets) have been extensively used as in vitro "minimal" cell models. In particular, simple and complex biomolecular reactions have been carried out inside these self-assembled micro- and nano-sized compartments, leading to the synthesis of RNA and functional proteins inside liposomes. Despite this experimental progress, a detailed physical understanding of the underlying dynamics is missing. In particular, the combination of solute compartmentalization, reactivity and stochastic effects has not yet been clarified. A combination of experimental and computational approaches can reveal interesting mechanisms governing the behavior of micro compartmentalized systems, in particular by highlighting the intrinsic stochastic diversity within a population of "synthetic cells".</p> <p>Methods</p> <p>In this context, we have developed a computational platform called ENVIRONMENT suitable for studying the stochastic time evolution of reacting lipid compartments. This software - which implements a Gillespie Algorithm - is an improvement over a previous program that simulated the stochastic time evolution of homogeneous, fixed-volume, chemically reacting systems, extending it to more general conditions in which a collection of similar such systems interact and change over the course of time. In particular, our approach is focused on elucidating the role of randomness in the time behavior of chemically reacting lipid compartments, such as micelles, vesicles or micro emulsions, in regimes where random fluctuations due to the stochastic nature of reacting events can lead an open system towards unexpected time evolutions.</p> <p>Results</p> <p>This paper analyses the so-called Ribocell (RNA-based cell) model. It consists in a hypothetical minimal cell based on a self-replicating minimum RNA genome coupled with a self-reproducing lipid vesicle compartment. This model assumes the existence of two ribozymes, one able to catalyze the conversion of molecular precursors into lipids and the second able to replicate RNA strands. The aim of this contribution is to explore the feasibility of this hypothetical minimal cell. By deterministic kinetic analysis, the best external conditions to observe synchronization between genome self-replication and vesicle membrane reproduction are determined, while its robustness to random fluctuations is investigated using stochastic simulations, and then discussed.</p

Machines on Genes: Enzymes that Make, Break and Move DNA and RNA

As the vital information repositories of the cell, the nucleic acids DNA and RNA pose many challenges as enzyme substrates. To produce, maintain and repair DNA and RNA, and to extract the genetic information that they encode, a battery of remarkable enzymes has evolved, which includes translocases, polymerases/replicases, helicases, nucleases, topoisomerases, transposases, recombinases, repair enzymes and ribosomes. An understanding of how these enzymes function is essential if we are to have a clear view of the molecular biology of the cell and aspire to manipulate genomes and gene expression to our advantage. To bring together scientists working in this fast-developing field, the Biochemical Society held a Focused Meeting, ‘Machines on Genes: Enzymes that Make, Break and Move DNA and RNA’, at Robinson College, University of Cambridge, U.K., in August 2009. The present article summarizes the research presented at this meeting and the reviews associated with the talks which are published in this issue of Biochemical Society Transactions

Potential regulatory interactions of Escherichia coli RraA protein with DEAD-box helicases.

Members of the DEAD-box family of RNA helicases contribute to virtually every aspect of RNA metabolism, in organisms from all domains of life. Many of these helicases are constituents of multicomponent assemblies, and their interactions with partner proteins within the complexes underpin their activities and biological function. In Escherichia coli the DEAD-box helicase RhlB is a component of the multienzyme RNA degradosome assembly, and its interaction with the core ribonuclease RNase E boosts the ATP-dependent activity of the helicase. Earlier studies have identified the regulator of ribonuclease activity A (RraA) as a potential interaction partner of both RNase E and RhlB. We present structural and biochemical evidence showing how RraA can bind to, and modulate the activity of RhlB and another E. coli DEAD-box enzyme, SrmB. Crystallographic structures are presented of RraA in complex with a portion of the natively unstructured C-terminal tail of RhlB at 2.8-Å resolution, and in complex with the C-terminal RecA-like domain of SrmB at 2.9 Å. The models suggest two distinct mechanisms by which RraA might modulate the activity of these and potentially other helicases

Los pacientes del hospital como recurso pedagógico irremplazable: "Todos los pacientes son neurológicos"

Con el advenimiento de la nueva tecnología es necesario prevenir una eventual distorsión en el proceso de enseñanza-aprendizaje en medicina, especialmente por erróneas suposiciones de carencia de pacientes para la realización de actividades prácticas. Situación que también ha sido detectada desde la actividad docente en nuestra Cátedra.Facultad de Ciencias Médica

Los pacientes del hospital como recurso pedagógico irremplazable: "Todos los pacientes son neurológicos"

Con el advenimiento de la nueva tecnología es necesario prevenir una eventual distorsión en el proceso de enseñanza-aprendizaje en medicina, especialmente por erróneas suposiciones de carencia de pacientes para la realización de actividades prácticas. Situación que también ha sido detectada desde la actividad docente en nuestra Cátedra.Facultad de Ciencias Médica