97 research outputs found
Symplastic scrotal leiomyoma: a case report
<p>Abstract</p> <p>Introduction</p> <p>Scrotal leiomyomas are rare tumours which are essentially benign. Recurrence and malignant transformation to leiomyosarcoma have been reported. However, a specific subgroup with increased bizarre nuclei showing increased mitosis raises the need for a closer follow-up. We report on such a case.</p> <p>Case presentation</p> <p>We report the case of a 65-year-old man who underwent a scrotal lump excision. Histology showed a well defined leiomyoma. The presence of nuclear pleomorphism and mitoses, just falling short of the criteria for malignancy, made prediction of biological behaviour difficult. The patient remains well on 4-year follow-up.</p> <p>Conclusion</p> <p>Histological evidence of increased mitosis raises the need for sustained follow-up in view of the malignant potential from the extent of mitosis. Immunohistochemistry helps in identifying those patients warranting close follow-up.</p
Evolution of Robustness to Noise and Mutation in Gene Expression Dynamics
Phenotype of biological systems needs to be robust against mutation in order
to sustain themselves between generations. On the other hand, phenotype of an
individual also needs to be robust against fluctuations of both internal and
external origins that are encountered during growth and development. Is there a
relationship between these two types of robustness, one during a single
generation and the other during evolution? Could stochasticity in gene
expression have any relevance to the evolution of these robustness? Robustness
can be defined by the sharpness of the distribution of phenotype; the variance
of phenotype distribution due to genetic variation gives a measure of `genetic
robustness' while that of isogenic individuals gives a measure of
`developmental robustness'. Through simulations of a simple stochastic gene
expression network that undergoes mutation and selection, we show that in order
for the network to acquire both types of robustness, the phenotypic variance
induced by mutations must be smaller than that observed in an isogenic
population. As the latter originates from noise in gene expression, this
signifies that the genetic robustness evolves only when the noise strength in
gene expression is larger than some threshold. In such a case, the two
variances decrease throughout the evolutionary time course, indicating increase
in robustness. The results reveal how noise that cells encounter during growth
and development shapes networks' robustness to stochasticity in gene
expression, which in turn shapes networks' robustness to mutation. The
condition for evolution of robustness as well as relationship between genetic
and developmental robustness is derived through the variance of phenotypic
fluctuations, which are measurable experimentally.Comment: 25 page
An Analytically Solvable Model for Rapid Evolution of Modular Structure
Biological systems often display modularity, in the sense that they can be
decomposed into nearly independent subsystems. Recent studies have suggested
that modular structure can spontaneously emerge if goals (environments) change
over time, such that each new goal shares the same set of sub-problems with
previous goals. Such modularly varying goals can also dramatically speed up
evolution, relative to evolution under a constant goal. These studies were based
on simulations of model systems, such as logic circuits and RNA structure, which
are generally not easy to treat analytically. We present, here, a simple model
for evolution under modularly varying goals that can be solved analytically.
This model helps to understand some of the fundamental mechanisms that lead to
rapid emergence of modular structure under modularly varying goals. In
particular, the model suggests a mechanism for the dramatic speedup in evolution
observed under such temporally varying goals
Specialization Can Drive the Evolution of Modularity
Organismal development and many cell biological processes are organized in a modular fashion, where regulatory molecules form groups with many interactions within a group and few interactions between groups. Thus, the activity of elements within a module depends little on elements outside of it. Modularity facilitates the production of heritable variation and of evolutionary innovations. There is no consensus on how modularity might evolve, especially for modules in development. We show that modularity can increase in gene regulatory networks as a byproduct of specialization in gene activity. Such specialization occurs after gene regulatory networks are selected to produce new gene activity patterns that appear in a specific body structure or under a specific environmental condition. Modules that arise after specialization in gene activity comprise genes that show concerted changes in gene activities. This and other observations suggest that modularity evolves because it decreases interference between different groups of genes. Our work can explain the appearance and maintenance of modularity through a mechanism that is not contingent on environmental change. We also show how modularity can facilitate co-option, the utilization of existing gene activity to build new gene activity patterns, a frequent feature of evolutionary innovations
Proportionality between variances in gene expression induced by noise and mutation: consequence of evolutionary robustness
<p>Abstract</p> <p>Background</p> <p>Characterization of robustness and plasticity of phenotypes is a basic issue in evolutionary and developmental biology. The robustness and plasticity are concerned with changeability of a biological system against external perturbations. The perturbations are either genetic, i.e., due to mutations in genes in the population, or epigenetic, i.e., due to noise during development or environmental variations. Thus, the variances of phenotypes due to genetic and epigenetic perturbations provide quantitative measures for such changeability during evolution and development, respectively.</p> <p>Results</p> <p>Using numerical models simulating the evolutionary changes in the gene regulation network required to achieve a particular expression pattern, we first confirmed that gene expression dynamics robust to mutation evolved in the presence of a sufficient level of transcriptional noise. Under such conditions, the two types of variances in the gene expression levels, i.e. those due to mutations to the gene regulation network and those due to noise in gene expression dynamics were found to be proportional over a number of genes. The fraction of such genes with a common proportionality coefficient increased with an increase in the robustness of the evolved network. This proportionality was generally confirmed, also under the presence of environmental fluctuations and sexual recombination in diploids, and was explained from an evolutionary robustness hypothesis, in which an evolved robust system suppresses the so-called error catastrophe - the destabilization of the single-peaked distribution in gene expression levels. Experimental evidences for the proportionality of the variances over genes are also discussed.</p> <p>Conclusions</p> <p>The proportionality between the genetic and epigenetic variances of phenotypes implies the correlation between the robustness (or plasticity) against genetic changes and against noise in development, and also suggests that phenotypic traits that are more variable epigenetically have a higher evolutionary potential.</p
An End to Endless Forms: Epistasis, Phenotype Distribution Bias, and Nonuniform Evolution
Studies of the evolution of development characterize the way in which gene
regulatory dynamics during ontogeny constructs and channels phenotypic
variation. These studies have identified a number of evolutionary regularities:
(1) phenotypes occupy only a small subspace of possible phenotypes, (2) the
influence of mutation is not uniform and is often canalized, and (3) a great
deal of morphological variation evolved early in the history of multicellular
life. An important implication of these studies is that diversity is largely the
outcome of the evolution of gene regulation rather than the emergence of new,
structural genes. Using a simple model that considers a generic property of
developmental maps—the interaction between multiple genetic elements
and the nonlinearity of gene interaction in shaping phenotypic
traits—we are able to recover many of these empirical regularities. We
show that visible phenotypes represent only a small fraction of possibilities.
Epistasis ensures that phenotypes are highly clustered in morphospace and that
the most frequent phenotypes are the most similar. We perform phylogenetic
analyses on an evolving, developmental model and find that species become more
alike through time, whereas higher-level grades have a tendency to diverge.
Ancestral phenotypes, produced by early developmental programs with a low level
of gene interaction, are found to span a significantly greater volume of the
total phenotypic space than derived taxa. We suggest that early and late
evolution have a different character that we classify into micro- and
macroevolutionary configurations. These findings complement the view of
development as a key component in the production of endless forms and highlight
the crucial role of development in constraining biotic diversity and
evolutionary trajectories
Microanatomic Distribution of Myeloid Heme Oxygenase-1 Protects against Free Radical-Mediated Immunopathology in Human Tuberculosis
Heme oxygenase-1 (HO-1) is a cytoprotective enzyme that controls inflammatory responses and redox homeostasis; however, its role during pulmonary tuberculosis (TB) remains unclear. Using freshly resected human TB lung tissue, we examined the role of HO-1 within the cellular and pathological spectrum of TB. Flow cytometry and histopathological analysis of human TB lung tissues showed that HO-1 is expressed primarily in myeloid cells and that HO-1 levels in these cells were directly proportional to cytoprotection. HO-1 mitigates TB pathophysiology by diminishing myeloid cell-mediated oxidative damage caused by reactive oxygen and/or nitrogen intermediates, which control granulocytic karyorrhexis to generate a zonal HO-1 response. Using whole-body or myeloid-specific HO-1-deficient mice, we demonstrate that HO-1 is required to control myeloid cell infiltration and inflammation to protect against TB progression. Overall, this study reveals that zonation of HO-1 in myeloid cells modulates free-radical-mediated stress, which regulates human TB immunopathology
Anterior surgical management of the cervicothoracic junction lesions at T1 and T2 vertebral bodies
Clinical characteristics and prognosis of osteosarcoma in young children: a retrospective series of 15 cases
<p>Abstract</p> <p>Background</p> <p>Osteosarcoma is the most common primary bone malignancy in childhood and adolescence. However, it is very rare in children under 5 years of age. Although studies in young children are limited in number, they all underline the high rate of amputation in this population, with conflicting results being recently reported regarding their prognosis.</p> <p>Methods</p> <p>To enhance knowledge on the clinical characteristics and prognosis of osteosarcoma in young children, we reviewed the medical records and histology of all children diagnosed with osteosarcoma before the age of five years and treated in SFCE (Société Française des Cancers et leucémies de l'Enfant) centers between 1980 and 2007.</p> <p>Results</p> <p>Fifteen patients from 7 centers were studied. Long bones were involved in 14 cases. Metastases were present at diagnosis in 40% of cases. The histologic type was osteoblastic in 74% of cases. Two patients had a relevant history. One child developed a second malignancy 13 years after osteosarcoma diagnosis.</p> <p>Thirteen children received preoperative chemotherapy including high-dose methotrexate, but only 36% had a good histologic response. Chemotherapy was well tolerated, apart from a case of severe late convulsive encephalopathy in a one-year-old infant. Limb salvage surgery was performed in six cases, with frequent mechanical and infectious complications and variable functional outcomes.</p> <p>Complete remission was obtained in 12 children, six of whom relapsed. With a median follow-up of 5 years, six patients were alive in remission, seven died of their disease (45%), in a broad range of 2 months to 8 years after diagnosis, two were lost to follow-up.</p> <p>Conclusions</p> <p>Osteosarcoma seems to be more aggressive in children under five years of age, and surgical management remains a challange.</p
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