123 research outputs found
Computing hierarchical transition graphs of asynchronous genetic regulatory networks
In the field of theoretical biology the study of the dynamics of the so-called gene regulatory networks is useful to follow the relationship between the expression of a gene and its dynamic regulatory effect on the cell fate. To date, most of the models developed for this purpose, applies the synchronous update schedule while reality is far from being so. On the other hand, the more realistic asynchronous update requires to compute all possible updates at each single instant, thus bearing a much greater computational load. In the present work, we describe a novel method that addresses the problem of efficiently exploring the dynamics of a gene regulatory network with the asynchronous update
Essentiality is an emergent property of metabolic network wiring
The topological bases of essentiality in the yeast metabolic network from the perspective of double mutations are the subject of this study. A strong relationship between essentiality and the ‘missing alternative’ topological property is shown in terms of the presence of multiple genes synthesizing the same enzyme, supplementary enzymes participating in the same metabolic reaction, and availability of other pathways in the graph connecting the separated nodes after the knockouts. We demonstrate that the ‘missing alternative’ paradigm is sufficient to explain the generation of essentiality for double mutations in which each single deleted element is non-essential
Functional essentiality from topology features in metabolic networks: A case study in yeast
The relation between the position of mutations in Saccharomyces cerevisiae metabolic network and their lethality is the subject of this work. We represent the topology of the network by a directed graph: nodes are metabolites and arcs represent the reactions; a mutation corresponds to the removal of all the arcs referring to the deleted enzyme. Using publicly available knock-out data, we show that lethality corresponds to the lack of alternative paths in the perturbed network linking the nodes affected by the enzyme deletion. Such feature is at the basis of the recently recognized importance of 'marginal' arcs of metabolic networks. (c) 2005 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved
Anesthetic Management during Cesarean Section in English Bulldogs
The authors describe their experience with the management of the perioperative period, general anesthesia and the
postoperative period in English bulldogs undergoing elective cesarean section and its effect on the neonates. The anesthetist for
animals undergoing cesarean operation must be aware of any special needs, not only of the patient undergoing surgery, but also of
the neonates. Anesthetic drugs administered to the pregnant patient will readily cross the placenta and affect them, with the exception
of local anesthetics. Pregnant female patients are at increased anesthetic risk due to pregnancy-associated physiological alterations,
such as altered pulmonary function. The anesthetist is often called to perform anesthesia on brachycephalic dogs for an elective
cesarean section. Due to their conformation, these animals may have one or more anatomical abnormalities of the upper airways,
which compromise the ability to ventilate adequately. The induction and recovery phases of anesthesia can be extremely dangerous
in these patients, but the maintenance phase is generally fairly straightforward because the airways are controlled during maintenance.
In addition, vagal tone is frequently high and this can contribute towards significant bradycardia and further airway narrowing. All
these reasons make general anesthesia in brachycephalic dogs undergoing cesarean section rather complicated
Collective behavior in gene regulation: Post-transcriptional regulation and the temporal compartmentalization of cellular cycles
Self-sustained oscillations are perhaps the most studied objects in science. The accomplishment of such a task reliably and accurately requires the presence of specific control mechanisms to face the presence of variable and largely unpredictable environmental stimuli and noise. Self-sustained oscillations of transcript abundance are, in fact, widespread and are not limited to the reproductive cycle but are also observed during circadian rhythms, metabolic cycles, developmental cycles and so on. To date, much of the literature has focused on the transcriptional machinery underlying control of the basic timing of transcript abundance. However, mRNA abundance is known to be regulated at the post-transcriptional level also and the relative contribution of the two mechanisms to gene-expression programmes is currently a major challenge in molecular biology. Here, we review recent results showing the relevance of the post-transcriptional regulation layer and present a statistical reanalysis of the yeast metabolic cycle using publicly available gene-expression and RNA-binding data. Taken together, the recent theoretical and experimental developments reviewed and the results of our reanalysis strongly indicate that regulation of mRNA stability is a widespread, phase-specific and finely tuned mechanism for the multi-layer control of gene expression needed to achieve high flexibility and adaptability to external and internal signals
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The Sam-Sam interaction between Ship2 and the EphA2 receptor: Design and analysis of peptide inhibitors
AbstractThe lipid phosphatase Ship2 represents a drug discovery target for the treatment of different diseases, including cancer. Its C-terminal sterile alpha motif domain (Ship2-Sam) associates with the Sam domain from the EphA2 receptor (EphA2-Sam). This interaction is expected to mainly induce pro-oncogenic effects in cells therefore, inhibition of the Ship2-Sam/EphA2-Sam complex may represent an innovative route to discover anti-cancer therapeutics. In the present work, we designed and analyzed several peptide sequences encompassing the interaction interface of EphA2-Sam for Ship2-Sam. Peptide conformational analyses and interaction assays with Ship2-Sam conducted through diverse techniques (CD, NMR, SPR and MST), identified a positively charged penta-amino acid native motif in EphA2-Sam, that once repeated three times in tandem, binds Ship2-Sam. NMR experiments show that the peptide targets the negatively charged binding site of Ship2-Sam for EphA2-Sam. Preliminary in vitro cell-based assays indicate that -at 50 µM concentration- it induces necrosis of PC-3 prostate cancer cells with more cytotoxic effect on cancer cells than on normal dermal fibroblasts. This work represents a pioneering study that opens further opportunities for the development of inhibitors of the Ship2-Sam/EphA2-Sam complex for therapeutic applications.</jats:p
Use of Nanohydroxyapatite in regenerative therapy in dogs affected by periodontopathy: preliminary results
Nanosized ceramics may represent a promising class of bone graft substitutes due to their improved osseointegrative and osseoinductive properties. Nanohydroxyapatite binds itself to the bone and favours bone healing by stimulation of osteoblast activity (Singh et al., 2012). The present study aims to analyse the in vivo behaviour of nanohydroxyapatite and to assess its regenerative capacity in dogs affected by periodontal disease.
Twenty-eight dogs of different breeds, aged between 5 and 15 years, were employed in the study and were randomly subdivided into a control group and an experimental group. After clinical, instrumental and radiological examinations to estimate the severity of the disease, all the subjects underwent dental prophylaxis and a bioptic sample was taken. A histopathological examination of the periodontal tissues, in correspondence with teeth with periodontopathy ranging between grades II and III, followed. Regenerative therapy with applications of nanohydroxyapatite was administered only to the dogs of the experimental group. After a period of between 30 and 42 days, a further clinical, instrumental and radiological examination was carried out and a bioptic sample taken solely on the dogs whose histological examinations showed changes ascribable to periodontal disease.
The results of the histopathological examination demonstrated that the subjects belonging to the control group, who only underwent the dental prophylaxis, in no case showed any histopathological improvement. In 6 out of 14 cases, the situation remained stationary and in the remaining 8 there was a clear deterioration. On the contrary, all the dogs in the experimental group, who underwent dental prophylaxis together with the administration of nanohydroxyapatite, showed clear signs of improvement with respect to their initial condition. Furthermore, there was no sign of any inflammatory reaction in the areas which had been treated with nanohydroxyapatite.
In conclusion the study demonstrated the regenerative potential of nanohydroxyapatite in periodontal therapy. In fact, its use as a graft material has produced very satisfactory results, which have been supported without doubt by the histopathological examinations. Thus, nanohydroxyapatite represents a valid osteoconductive and osteoinductive graft product in dogs. However, more research is needed and it is, therefore, imperative to extend the case histories and further standardize diagnostic methods.
Singh VP, Nayak DG, Uppoor AS, Shah D: Clinical and radiographic evaluation of Nano-crystalline hydroxyapatite bone graft (Sybograf) in combination with bioresorbable collagen membrane (Periocol) in periodontal intrabony defects. Dental Research Journal, 2012; 9: 60-67
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