891 research outputs found
Crystal structure of the Escherichia coli RNA degradosome component enolase.
The crystal structure of Escherichia coli enolase (EC 4.2.1.11, phosphopyruvate hydratase), which is a component of the RNA degradosome, has been determined at 2.5 Å. There are four molecules in the asymmetric unit of the C2 cell, and in one of the molecules, flexible loops close onto the active site. This closure mimics the conformation of the substrate-bound intermediate. A comparison of the structure of the E. coli enolase with the eukaryotic enolase structures available (lobster and yeast) indicates a high degree of conservation of the hydrophobic core and the subunit interface of this homodimeric enzyme. The dimer interface is enriched in charged residues compared with other protein homodimers, which may explain our observations from analytical ultracentrifugation that dimerisation is affected by ionic strength. The putative role of enolase in the RNA degradosome is discussed; although it was not possible to ascribe a specific role to it, a structural role is possible.http://dx.doi.org
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
STEM materials: a new frontier for an intelligent sustainable world
Materials are addressed as possible enablers for solutions to many global societal challenges. A foresight exercise has been conducted to identify research paths to design, with a new approach, a generation of materials which can provide multi-functionalities. These material systems have been named ???stem???, in analogy to living cells where a base of primitive units can be designed and assembled for self-reacting to external inputs. These materials will embed a concept of ???internet in things???, where their processing capacity will enable the systems to interact with the environment and express diverse functionalities. Stem materials do not exist yet, but many clues from diferent theoretical and experimental results suggest they can be developed, and because living organisms exist. This article aims at launching this new approach and promoting the structuring of a multi-disciplinary community to fll the research gaps
A spatial model of autocatalytic reactions
Biological cells with all of their surface structure and complex interior
stripped away are essentially vesicles - membranes composed of lipid bilayers
which form closed sacs. Vesicles are thought to be relevant as models of
primitive protocells, and they could have provided the ideal environment for
pre-biotic reactions to occur. In this paper, we investigate the stochastic
dynamics of a set of autocatalytic reactions, within a spatially bounded
domain, so as to mimic a primordial cell. The discreteness of the constituents
of the autocatalytic reactions gives rise to large sustained oscillations, even
when the number of constituents is quite large. These oscillations are
spatio-temporal in nature, unlike those found in previous studies, which
consisted only of temporal oscillations. We speculate that these oscillations
may have a role in seeding membrane instabilities which lead to vesicle
division. In this way synchronization could be achieved between protocell
growth and the reproduction rate of the constituents (the protogenetic
material) in simple protocells.Comment: Submitted to Phys. Rev.
Evaluation of ticarcillin/clavulanic acid versus ceftriaxone plus amikacin for fever and neutropenia in pediatric patients with leukemia and lymphoma
BACKGROUND: The empirical use of antibiotic treatments is widely accepted as a means to treat cancer patients in chemotherapy who have fever and neutropenia. Intravenous monotherapy, with broad spectrum antibiotics, of patients with a high risk of complications is a possible alternative. METHODS: We conducted a prospective open-label, randomized study of patients with lymphoma or leukemia who had fever and neutropenia during chemotherapy. Patients received either monotherapy with ticarcillin/clavulanic acid (T) or ceftriaxone plus amikacin (C+A). RESULTS: Seventy patients who presented 136 episodes were evaluated, 68 in each arm of the study. The mean neutrophil counts at admission were 217cells/mm³ (T) and 201cells/mm³ (C+A). The mean duration of neutropenia was 8.7 days (T) and 7.6 days (C+A). Treatment was successful without the need for modifications in 71% of the episodes in the T group and 81% in the C+A group (p=0.23). Treatment was considered to have failed because of death in two episodes (3%) in the T group and three episodes (4%) in the C+A group, and because of a change in the drug applied in one episode in the T group and two episodes in the C+A group. Overall success was 96% (T) and 93% (C+A). Adverse events that occurred in group T were not related to the drugs used in this study. CONCLUSION: In pediatric and adolescent patients with leukemia or lymphoma, who presented with fever and neutropenia, during chemotherapy, ticarcillin/clavulanic acid was as successful as the combination of ceftriaxone plus amikacin. It should be considered an appropriate option for this group of patients at high risk for infections.Federal University of São Paulo Division of Infectious Disease Pediatric Oncology InstituteUNIFESP, Division of Infectious Disease Pediatric Oncology InstituteSciEL
7.000 AÑOS DE HISTORIA EN EL FIN DEL MUNDO
Se ha propuesto que las migraciones podrían expli-car cambios culturales identificados en el registro ar-queológico de Patagonia Austral, como el desarrollo de estrategias de aprovechamiento de recursos marinos y modificaciones en las herramientas utilizadas. El análisis del genoma de individuos de origen arqueológico revela una continuidad genética durante 6.600 años y sugiere que los movimientos poblacionales no explican la apari-ción de la adaptación marina, adquirida por desarrollo local o por transmisión cultural. Sin embargo, dos even-tos de migración posteriores estarían correlacionados con cambios vinculados a tecnologías líticas. Además, se observa que ocurrieron procesos de mestizaje entre grupos vecinos hace 1.500 años
On RAF Sets and Autocatalytic Cycles in Random Reaction Networks
The emergence of autocatalytic sets of molecules seems to have played an
important role in the origin of life context. Although the possibility to
reproduce this emergence in laboratory has received considerable attention,
this is still far from being achieved. In order to unravel some key properties
enabling the emergence of structures potentially able to sustain their own
existence and growth, in this work we investigate the probability to observe
them in ensembles of random catalytic reaction networks characterized by
different structural properties. From the point of view of network topology, an
autocatalytic set have been defined either in term of strongly connected
components (SCCs) or as reflexively autocatalytic and food-generated sets
(RAFs). We observe that the average level of catalysis differently affects the
probability to observe a SCC or a RAF, highlighting the existence of a region
where the former can be observed, whereas the latter cannot. This parameter
also affects the composition of the RAF, which can be further characterized
into linear structures, autocatalysis or SCCs. Interestingly, we show that the
different network topology (uniform as opposed to power-law catalysis systems)
does not have a significantly divergent impact on SCCs and RAFs appearance,
whereas the proportion between cleavages and condensations seems instead to
play a role. A major factor that limits the probability of RAF appearance and
that may explain some of the difficulties encountered in laboratory seems to be
the presence of molecules which can accumulate without being substrate or
catalyst of any reaction.Comment: pp 113-12
Role of electrostatic interactions in amyloid beta-protein (Abeta) oligomer formation: A discrete molecular dynamics study
Pathological folding and oligomer formation of the amyloid beta-protein
(Abeta) are widely perceived as central to Alzheimer's disease (AD).
Experimental approaches to study Abeta self-assembly are problematic, because
most relevant aggregates are quasi-stable and inhomogeneous. We apply a
discrete molecular dynamics (DMD) approach combined with a four-bead protein
model to study oligomer formation of the amyloid beta-protein (Abeta). We
address the differences between the two most common Abeta alloforms, Abeta40
and Abeta42, which oligomerize differently in vitro. We study how the presence
of electrostatic interactions (EIs) between pairs of charged amino acids
affects Abeta40 and Abeta42 oligomer formation. Our results indicate that EIs
promote formation of larger oligomers in both Abeta40 and Abeta42. The Abeta40
size distribution remains unimodal, whereas the Abeta42 distribution is
trimodal, as observed experimentally. Abeta42 folded structure is characterized
by a turn in the C-terminus that is not present in Abeta40. We show that the
same C-terminal region is also responsible for the strongest intermolecular
contacts in Abeta42 pentamers and larger oligomers. Our results suggest that
this C-terminal region plays a key role in the formation of Abeta42 oligomers
and the relative importance of this region increases in the presence of EIs.
These results suggest that inhibitors targeting the C-terminal region of
Abeta42 oligomers may be able to prevent oligomer formation or structurally
modify the assemblies to reduce their toxicity.Comment: Accepted for publication at Biophysical Journa
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