Heterogeneity in clinical features and disease severity in ataxia-associated SYNE1 mutations

The autosomal recessive spinocerebellar ataxias are an exciting field of study, with a growing number of causal genes and an expanding phenotypic spectrum. SYNE1 was originally discovered in 2007 as the causal gene underlying autosomal recessive spinocerebellar ataxia 1, a disease clinically thought to manifest with mainly pure cerebellar ataxia. Since the original report SYNE1 mutations have also been identified in families with motor neuronopathy and arthrogryposis but few families have been screened as the gene is very large at 146 exons in length. We screened 196 recessive and sporadic ataxia patients for mutations in SYNE1 using next generation sequencing in order to assess its frequency and extend the clinicogenetic spectrum. We identified four novel truncating mutations spread throughout the SYNE1 gene from three families living in London that originated from England, Turkey and Sri Lanka. The phenotype was mainly pure cerebellar ataxia in two families, cognitive decline was present in all three families, axonal neuropathy in one family and marked spasticity in the Turkish family, with a range of disease severities. Searching for genotype-phenotype correlations in the SYNE1 gene, defects located near the 3' prime end of the gene are more frequently associated with motor neuron or neuromuscular involvement so far. Our data indicate SYNE1 mutations are not an uncommon cause of recessive ataxia with or without additional clinical features in patients from various ethnicities. The use of next generation sequencing allows the rapid analysis of large genes and will likely reveal more SYNE1 associated cases and further expand genotype-phenotype correlations

Avaliação da organogênese in vitro do Clone 7 de Eucalyptus urograndis em diferentes meios de cultura.

Resumo

Prolactin-producing pituitary carcinoma, hypopituitarism, and graves' disease-Report of a challenging case and literature review

Introduction: The diagnosis of pituitary carcinoma is very rare, requires the evidence of metastatic disease, and has a poor overall survival. Malignant prolactinoma frequently requires dopamine agonist therapy, pituitary surgery, radiotherapy, and even chemotherapy. Case description: A 19-year-old female presented with galactorrhea, primary amenorrhea, and left hemianopsia. Complementary study detected hyperprolactinemia and a pituitary macroadenoma with cavernous sinus invasion and suprasellar growth. She was treated with cabergoline and bromocriptine without clinical or analytical improvement. Resection of the pituitary lesion was programmed and a non-contiguous lesion of the nasal mucosa was detected during the approach. This metastasis led to the diagnosis of prolactin-producing pituitary carcinoma. After partial resection, the patient was submitted to radiotherapy for residual disease with persistent symptoms. She developed growth hormone deficiency, central hypothyroidism, hypogonadism, and permanent diabetes insipidus. Six years later she was admitted for the suspicion of secondary adrenal insufficiency and thyrotoxicosis. Physical findings, laboratory data, thyroid ultrasound, and scintigraphy achieved the diagnosis of Graves' disease and hypocortisolism. She was treated with hydrocortisone and methimazole, but central hypothyroidism recurred after antithyroid drug withdrawal. Nine years after the diagnosis of a pituitary carcinoma, she maintains treatment with bromocriptine, has a locally stable disease, with no metastases. Conclusion: This report highlights an unusual presentation of a prolactin-producing pituitary carcinoma in a young female. The patient had multiple hormone deficiencies due to a pituitary lesion and treatments. The posterior development of hyperthyroidism and adrenal insufficiency brought an additional difficulty to the approach

Interaction between vortices in models with two order parameters

The interaction energy and force between widely separated strings is analyzed in a field theory having applications to superconducting cosmic strings, the SO(5) model of high-temperature superconductivity, and solitons in nonlinear optics. The field theory has two order parameters, one of which is broken in the vacuum (giving rise to strings), the other of which is unbroken in the vacuum but which could nonetheless be broken in the core of the string. If this does occur, there is an effect on the energetics of widely separated strings. This effect is important if the length scale of this second order parameter is longer than that of the other fields in the problem.Comment: 11 pages, 3 figures. Minor changes in the text. Accepted for publication in Phys. Rev.

High-Sensitivity Troponin T: A Biomarker for Diuretic Response in Decompensated Heart Failure Patients

Background. Patients presenting with acutely decompensated heart failure (ADHF) and positive circulating cardiac troponins were found to be a high-risk cohort. The advent of high-sensitive troponins resulted in a detection of positive troponins in a great proportion of heart failure patients. However, the pathophysiological significance of this phenomenon is not completely clear. Objectives. The aim of this study is to determine the early evolution and clinical significance of high-sensitivity troponin T (hsTnT) in ADHF. Methods. Retrospective, secondary analysis of a prospective study including 100 patients with ADHF. Results. Globally, high-sensitivity troponin T decreased from day 1 to day 3 (P = 0,039). However, in the subgroup of patients who remained decompensated no significant differences in hsTnT from day 1 to day 3 were observed (P = 0,955), whereas in successfully compensated patients a significant reduction in hsTnT levels was observed (P = 0,025). High-sensitivity troponin T decrease was correlated with NTproBNP reduction (P = 0,007). Patients with hsTnT increase had longer length of stay (P = 0,033). Conclusions. Episodes of ADHF are associated with transient increases in the blood levels of hsTnT that are reduced with effective acute episode treatment. The decrease in hsTnT can translate less myocardial damage along with favourable ADHF treatment

Scaling of Hunter Gatherer Camp Size and Human Sociality

One of the most commonly-observed properties of human settlements, both past and present, is the tendency for larger settlements to display higher population densities. Work in urban science and archaeology suggests this densification pattern reflects an emergent spatial equilibrium where individuals balance movement costs with social interaction benefits, leading to increases in aggregate productivity and social interdependence. In this context, it is perhaps not surprising that the more temporary camps created by mobile hunters and gatherers exhibit a tendency to become less dense with their population size. Here we examine why this difference occurs and consider conditions under which hunter-gatherer groups may transition to sedentism and densification. We investigate the relationship between population and area in mobile hunter-gatherer camps using a dataset, representing a large cross-cultural sample, derived from the ethnographic literature. We present a model based on the interplay between social interactions and scalar stress for the relationship between camp area and group size that describes the observed patterns among mobile hunter-gatherers. The model highlights the tradeoffs between the costs and benefits of proximity and interaction that are common to all human aggregations and specifies the constraints that must be overcome for economies of scale and cooperation to emerge

In vitro organogenesis of Eucalyptus urophylla x E. grandis in three culture media.

Resumo. Brasil Biotec

Winding Number Correlation Functions and Cosmic String Formation

We develop winding number correlation functions that allow us to assess the role of field fluctuations on vortex formation in an Abelian gauge theory. We compute the behavior of these correlation functions in simple circumstances and show how fluctuations are important in the vicinity of the phase transition. We further show that, in our approximation, the emerging population of long/infinite string is produced by the classical dynamics of the fields alone, being essentially unaffected by field fluctuations.Comment: Latex file, 27 pages. 8 figures, available in compressed form by anonymous ftp from ftp://euclid.tp.ph.ic.ac.uk/papers/94-5_39.fig Latex and postscript versions also available at http://euclid.tp.ph.ic.ac.uk/Papers/index.htm