The effect of differences in methodology among some recent applications of shearing quotients.

A shearing quotient (SQ) is a way of quantitatively representing the Phase I shearing edges on a molar tooth. Ordinary or phylogenetic least squares regression is fit to data on log molar length (independent variable) and log sum of measured shearing crests (dependent variable). The derived linear equation is used to generate an 'expected' shearing crest length from molar length of included individuals or taxa. Following conversion of all variables to real space, the expected value is subtracted from the observed value for each individual or taxon. The result is then divided by the expected value and multiplied by 100. SQs have long been the metric of choice for assessing dietary adaptations in fossil primates. Not all studies using SQ have used the same tooth position or crests, nor have all computed regression equations using the same approach. Here we focus on re-analyzing the data of one recent study to investigate the magnitude of effects of variation in 1) shearing crest inclusion, and 2) details of the regression setup. We assess the significance of these effects by the degree to which they improve or degrade the association between computed SQs and diet categories. Though altering regression parameters for SQ calculation has a visible effect on plots, numerous iterations of statistical analyses vary surprisingly little in the success of the resulting variables for assigning taxa to dietary preference. This is promising for the comparability of patterns (if not casewise values) in SQ between studies. We suggest that differences in apparent dietary fidelity of recent studies are attributable principally to tooth position examined.

Molecular-assisted immunohistochemical optimization

Immunohistochemistry (IHC) is an essential tool in diagnostic surgical pathology, allowing analysis of protein subcellular localization The use of IHC by different laboratories has lead to inconsistencies in published literature for several antibodies, due to either interpretative (inter-observer venation) or technical reasons These disparities have major implications in both clinical and research settings In this study, we report our experience conducting an IHC optimization of antibodies against five proteins previously identified by proteomic analysis to be breast cancer biomarkers, namely 6PGL (PGLS), CAZ2 (CAPZA2), PA2G4 (EBP1) PSD2 and TKT Large variations in the immunolocalizations and intensities were observed when manipulating the antigen retrieval method and primary antibody incubation concentration However, the use of an independent molecular analysis method provided a clear indication in choosing the appropriate biologically and functionally relevant

Disassembly of a Medial Transenvelope Structure by Antibiotics during Intracellular Division.

Chlamydiales possess a minimal but functional peptidoglycan precursor biosynthetic and remodeling pathway involved in the assembly of the division septum by an atypical cytokinetic machine and cryptic or modified peptidoglycan-like structure (PGLS). How this reduced cytokinetic machine collectively coordinates the invagination of the envelope has not yet been explored in Chlamydiales. In other Gram-negative bacteria, peptidoglycan provides anchor points that connect the outer membrane to the peptidoglycan during constriction using the Pal-Tol complex. Purifying PGLS and associated proteins from the chlamydial pathogen Waddlia chondrophila, we unearthed the Pal protein as a peptidoglycan-binding protein that localizes to the chlamydial division septum along with other components of the Pal-Tol complex. Together, our PGLS characterization and peptidoglycan-binding assays support the notion that diaminopimelic acid is an important determinant recruiting Pal to the division plane to coordinate the invagination of all envelope layers with the conserved Pal-Tol complex, even during osmotically protected intracellular growth.

Clinical and biochemical responses after Gamma Knife surgery for a dopamine-secreting paraganglioma: case report.

The efficacy of Gamma Knife surgery (GKS) in local tumor control of non-secreting paragangliomas (PGLs) has been fully described by previous studies. However, with regard to secreting PGL, only one previous case report exists advocating its efficacy at a biological level. The aims of this study were: 1) to evaluate the safety/efficacy of GKS in a dopamine-secreting PGL; 2) to investigate whether the biological concentrations of free methoxytyramine could be used as a marker of treatment efficacy during the follow-up. We describe the case of a 62-year-old man diagnosed with left PGL. He initially underwent complete surgical excision. Thirty months after, he developed recurrent biological and neuroradiological disease; the most sensitive biomarker for monitoring the disease, concentration of plasma free methoxytyramine, started to increase. GKS was performed at a maximal marginal dose of 16 Gy. During the following 30 months, concentration of free methoxytyramine gradually decreased from 0.14 nmol/l (2*URL) before GKS to 0.09 nmol/l, 6 months after GKS and 0.07 nmol/l at the last follow-up after GKS (1.1*URL), confirming the efficacy of the treatment. Additionally, at 30 months there was approximately 36.6% shrinkage from the initial target volume. The GKS treatment was safe and effective, this being confirmed clinically, neuroradiologically and biologically. The case illustrates the importance of laboratory tests taking into account methoxytyramine when analyzing biological samples to assess the biochemical activity of a PGL. In addition, the identification of methoxytyramine as a unique positive biomarker could designate it for the monitoring of tumor relapse after treatments, including Gamma Knife surgery.

A pós-graduação lato sensu da UFPA no contexto da mercantilização da educação superior

Este trabalho teve por objetivo analisar o processo de mercantilização da educação superior, partindo do estudo dos cursos de pós-graduação lato sensu da Universidade Federal do Pará (UFPA), no período de 2008 a 2012. Entendemos que a pós-graduação lato sensu - PGLS ganhou destaque no Brasil para atender a uma demanda de profissionais carentes de qualificação, em nível superior, para atuar no mercado de trabalho. No entanto, a partir de 1990, a mesma ganha novos contornos, sendo desvinculada da CAPES e sem um órgão regulador que controle sua oferta, aliado ao fato de não ser atendida pela política educacional de pós-graduação. O cenário que se encontra em vigor é a oferta de cursos autofinanciados e conveniados, sendo mantidos mediante cobrança de mensalidades ou convênio com outras instituições. O fato gera algumas contradições, como no caso da legislação, para a Constituição Federal de 1988 estabelece que o ensino seja gratuito em estabelecimentos oficiais, no entanto, o Conselho Superior de Ensino, Pesquisa e Extensão da UFPA aprovou a Resolução UFPA nº 4.065/2010, regulamentando a oferta desses cursos, caracterizando assim uma das faces de adoção da lógica mercantil no interior dessa universidade pública. Para nossas análises e discussões, buscamos aproximações com o materialismo histórico-dialético e utilizamos como fonte de dados os documentos oficiais nacionais e institucionais, dados disponíveis no Sistema de Pós-Graduação On Line, Relatório de Gestão da UFPA, Pareceres de Aprovação, Projetos e Relatórios dos Cursos selecionados para compor a pesquisa, bem como entrevista semiestruturada com 10 sujeitos. Os resultados da pesquisa mostraram que dos 264 cursos lato sensu ofertados entre 2008 e 2012, 65,2% destes foram autofinanciados, 22,7% conveniados e 12,1% gratuitos. Além disso, foram identificados valores diferenciados no pagamento de hora-aula, nas mensalidades e despesas com coordenadores, principalmente entre cursos de uma mesma unidade acadêmica. Ademais, a análise da utilização dos recursos captados mostra que nos cursos autofinanciados a maioria das despesas são para pagamento de hora-aula, já os cursos conveniados destinam a maioria das receitas para manutenção dos cursos com passagens, diárias, material de escritório, e outros. Em síntese, o estudo mostra a consolidação da mercantilização da PGLS na UFPA, haja vista a rentabilidade que estes cursos propiciam, principalmente para determinadas áreas do conhecimento, seja mediante complementação salarial, seja na adequação dessa instituição à dinâmica capitalista atual no prevalecimento da lógica mercantil para a pós-graduação lato sensu.

SDHB loss predicts malignancy in pheochromocytomas/sympathethic paragangliomas, but not through hypoxia signalling

Prediction of malignant behaviour of pheochromocytomas/sympathetic paragangliomas (PCCs/PGLs) is very difficult if not impossible on a histopathological basis. In a familial setting, it is well known that succinate dehydrogenase subunit B (SDHB)-associated PCC/PGL very often metastasise. Recently, absence of SDHB expression as measured through immunohistochemistry was shown to be an excellent indicator of the presence of an SDH germline mutation in PCC/PGL. SDHB loss is believed to lead to tumour formation by activation of hypoxia signals. To clarify the potential use of SDHB immunohistochemistry as a marker of malignancy in PCC/PGL and its association with classic hypoxia signalling we examined SDHB, hypoxia inducible factor-1 (Hif-1 ) and its targets CA-9 and GLUT-1 expression on protein level using immunohistochemistry on a tissue micro array on a series of familial and sporadic tumours of 115 patients. Survival data was available for 66 patients. SDHB protein expression was lost in the tumour tissue of 12 of 99 patients. Of those 12 patients, 5 had an SDHB germline mutation, in 4 patients no germline mutation was detected and mutational status remained unknown in parts in 3 patients. Loss of SDHB expression was not associated with increased classic hypoxia signalling as detected by Hif-1 , CA-9 or GLUT-1 staining. Loss of SDHB expression was associated with an adverse outcome. The lack of correlation of SDHB loss with classic hypoxia signals argues against the current hypoxia hypothesis in malignant PCC/PGL. We suggest SDHB protein loss as a marker of adverse outcome both in sporadic and in familial PCC/PGL.

Malignant pheochromocytomas and paragangliomas: a diagnostic challenge

Malignant pheochromocytomas (PCCs) and paragangliomas (PGLs) are rare disorders arising from the adrenal gland, from the glomera along parasympathetic nerves or from paraganglia along the sympathetic trunk. According to the WHO classification, malignancy of PCCs and PGLs is defined by the presence of metastases at non-chromaffin sites distant from that of the primary tumor and not by local invasion. The overall prognosis of metastasized PCCs/PGLs is poor. Surgery offers currently the only change of cure. Preferably, the discrimination between malignant and benign PCCs/PGLs should be made preoperatively.

Data compilation of hummingbird-pollinated plant species in the Brazilian Atlantic rain forest

We studied the relationship between flower size and nectar properties of hummingbird-visited flowers in the Brazilian Atlantic Forest. We analysed the nectar volume and concentration as a function of corolla length and the average bill size of visitors for 150 plant species, using the phylogenetic generalized least squares (PGLS) to control for phylogenetic signals in the data. We found that nectar volume is positively correlated with corolla length due to phylogenetic allometry. We also demonstrated that larger flowers provide better rewards for long-billed hummingbirds. Regardless of the causal mechanisms, our results support the hypothesis that morphological floral traits that drive partitioning among hummingbirds correspond to the quantity of resources produced by the flowers in the Atlantic Forest. We demonstrate that the relationship between nectar properties and flower size is affected by phylogenetic constraints and thus future studies assessing the interaction between floral traits need to control for phylogenetic signals in the data.

Predictive gene lists for breast cancer prognosis: a topographic visualisation study

Background: The controversy surrounding the non-uniqueness of predictive gene lists (PGL) of small selected subsets of genes from very large potential candidates as available in DNA microarray experiments is now widely acknowledged 1. Many of these studies have focused on constructing discriminative semi-parametric models and as such are also subject to the issue of random correlations of sparse model selection in high dimensional spaces. In this work we outline a different approach based around an unsupervised patient-specific nonlinear topographic projection in predictive gene lists. Methods: We construct nonlinear topographic projection maps based on inter-patient gene-list relative dissimilarities. The Neuroscale, the Stochastic Neighbor Embedding(SNE) and the Locally Linear Embedding(LLE) techniques have been used to construct two-dimensional projective visualisation plots of 70 dimensional PGLs per patient, classifiers are also constructed to identify the prognosis indicator of each patient using the resulting projections from those visualisation techniques and investigate whether a-posteriori two prognosis groups are separable on the evidence of the gene lists. A literature-proposed predictive gene list for breast cancer is benchmarked against a separate gene list using the above methods. Generalisation ability is investigated by using the mapping capability of Neuroscale to visualise the follow-up study, but based on the projections derived from the original dataset. Results: The results indicate that small subsets of patient-specific PGLs have insufficient prognostic dissimilarity to permit a distinction between two prognosis patients. Uncertainty and diversity across multiple gene expressions prevents unambiguous or even confident patient grouping. Comparative projections across different PGLs provide similar results. Conclusion: The random correlation effect to an arbitrary outcome induced by small subset selection from very high dimensional interrelated gene expression profiles leads to an outcome with associated uncertainty. This continuum and uncertainty precludes any attempts at constructing discriminative classifiers. However a patient's gene expression profile could possibly be used in treatment planning, based on knowledge of other patients' responses. We conclude that many of the patients involved in such medical studies are intrinsically unclassifiable on the basis of provided PGL evidence. This additional category of 'unclassifiable' should be accommodated within medical decision support systems if serious errors and unnecessary adjuvant therapy are to be avoided.