Variations in PROKR2, But Not PROK2, Are Associated With Hypopituitarism and Septo-optic Dysplasia.

Context:Loss-of-function mutations in PROK2 and PROKR2 have been implicated in Kallmann syndrome (KS), characterized by hypogonadotropic hypogonadism and anosmia. Recent data suggest overlapping phenotypes/genotypes between KS and congenital hypopituitarism (CH), including septo-optic dysplasia (SOD).Objective:We screened a cohort of patients with complex forms of CH (n = 422) for mutations in PROK2 and PROKR2.Results:We detected 5 PROKR2 variants in 11 patients with SOD/CH: novel p.G371R and previously reported p.A51T, p.R85L, p.L173R, and p.R268C-the latter 3 being known functionally deleterious variants. Surprisingly, 1 patient with SOD was heterozygous for the p.L173R variant, whereas his phenotypically unaffected mother was homozygous for the variant. We sought to clarify the role of PROKR2 in hypothalamopituitary development through analysis of Prokr2(-/-) mice. Interestingly, these revealed predominantly normal hypothalamopituitary development and terminal cell differentiation, with the exception of reduced LH; this was inconsistent with patient phenotypes and more analogous to the healthy mother, although she did not have KS, unlike the Prokr2(-/-) mice.Conclusions:The role of PROKR2 in the etiology of CH, SOD, and KS is uncertain, as demonstrated by no clear phenotype-genotype correlation; loss-of-function variants in heterozygosity or homozygosity can be associated with these disorders. However, we report a phenotypically normal parent, homozygous for p.L173R. Our data suggest that the variants identified herein are unlikely to be implicated in isolation in these disorders; other genetic or environmental modifiers may also impact on the etiology. Given the phenotypic variability, genetic counseling may presently be inappropriate.

The structural effects of divalent cations and insulin on phospholipid model membranes /

It is well accepted that structural studies with model membranes are of considerable value in understanding the structure of biological membranes. Many studies with models of pure phospholipids have been done; but the effects of divalent cations and protein on these models would make these studies more applicable to intact membrane. The present study, performed with above view, is a structural analysis of divalent io~cardio1ipin complexes using the technique of x-ray diffraction. Cardiolipin, precipitated from dilute solution by divalent ionscalcium, magnesium and barium, contains little water and the structure formed is similar to the structure of pure cardiolipin with low water content. The calcium-cardiolipin complex forms a pure hexagonal type II phase that exists from 40 to 400 C. The molar ratio of calcium and cardiolipin in the complex is 1 : 1. Cardiolipin, precipitated with magnesium and barium forms two co-existing phases, lamellar and hexagonal, the relative quantity of the two phases being dependent on temperature. The hexagonal phase type II consisting of water filled channels formed by adding calcium to cardiolipin may have a remarkable permeability property in intact membrane. Pure cardiolipin and insulin at pH 3.0 and 4.0 precipitate but form no organised structure. Lecithin/cardiolipin and insulin precipitated at pH 3.0 give a pure lamellar phase. As the lecithin/cardiolipin molar ratio changes from 93/7 to SO/50, (a) the repeat distance of the lamellar changes from 72.8 X to 68.2 A; (b) the amount of protein bound increases in such a way that cardiolipin/insulin molar ratio in the complex reaches a maximum constant value at lecithin/cardiolipin molar ratio 70/30. A structural model based on these data shows that the molecular arrangement of lipid and protein is a lipid bilayer coated with protein molecules. The lipid-protein interaction is chiefly electrostatic and little, if any, hydrophobic bonding occurs in this particular system. So, the proposed model is essentially the same as Davson-Daniellifs model of biological membrane.

fMRI evidence for the involvement of the procedural memory system in morphological processing of a second language

Behavioural evidence suggests that English regular past tense forms are automatically decomposed into their stem and affix (played  = play+ed) based on an implicit linguistic rule, which does not apply to the idiosyncratically formed irregular forms (kept). Additionally, regular, but not irregular inflections, are thought to be processed through the procedural memory system (left inferior frontal gyrus, basal ganglia, cerebellum). It has been suggested that this distinction does not to apply to second language (L2) learners of English; however, this has not been tested at the brain level. This fMRI study used a masked-priming task with regular and irregular prime-target pairs (played-play/kept-keep) to investigate morphological processing in native and highly proficient late L2 English speakers. No between-groups differences were revealed. Compared to irregular pairs, regular pairs activated the pars opercularis, bilateral caudate nucleus and the right cerebellum, which are part of the procedural memory network and have been connected with the processing of morphologically complex forms. Our study is the first to provide evidence for native-like involvement of the procedural memory system in processing of regular past tense by late L2 learners of English.

A network of integrate and fire neurons for visual selection

Biological systems have facility to capture salient object(s) in a given scene, but it is still a difficult task to be accomplished by artificial vision systems. In this paper a visual selection mechanism based on the integrate and fire neural network is proposed. The model not only can discriminate objects in a given visual scene, but also can deliver focus of attention to the salient object. Moreover, it processes a combination of relevant features of an input scene, such as intensity, color, orientation, and the contrast of them. In comparison to other visual selection approaches, this model presents several interesting features. It is able to capture attention of objects in complex forms, including those linearly nonseparable. Moreover, computer simulations show that the model produces results similar to those observed in natural vision systems.

Sperm storage structures in the ovary of Helicolenus dactylopterus dactylopterus (Teleostei : Scorpaenidae): An ultrastructural study

The ultrastructure of ovarian sperm storage of Helicolenus dactylopterus dactylopterus is described, before and after the spawning period. The spermatozoa remain inside cryptal structures that are situated in the interlamellar gaps and are connected to the ovarian lumen by a duct. This complex forms a highly specialised structure. During the long storage period, crypts are richly vascularised. Their surrounding simple epithelia have intercellular junctions that may serve to protect the spermatozoa from the female immune system. At the moment during which insemination of mature oocytes occurs, the sperm may be expelled from cryptal structures by means of a spasmodic contraction. During the post spawning period, residual spermatozoa that remain in the crypts are eliminated by cryptal phagocytes. At the end of the process the crypts contain only an amorphous material.

Thrombomodulin-independent activation of protein C and specificity of hemostatically active snake venom serine proteinases - Crystal structures of native and inhibited Agkistrodon contortrix contortrix protein C activator

Protein C activation initiated by the thrombin-thrombomodulin complex forms the major physiological anticoagulant pathway. Agkistrodon contortrix contortrix protein C activator, a glycosylated single-chain serine proteinase, activates protein C without relying on thrombomodulin. The crystal structures of native and inhibited Agkistrodon contortrix contortrix protein C activator determined at 1.65 and 1.54 angstrom resolutions, respectively, indicate the pivotal roles played by the positively charged belt and the strategic positioning of the three carbohydrate moieties surrounding the catalytic site in protein C recognition, binding, and activation. Structural changes in the benzamidine-inhibited enzyme suggest a probable function in allosteric regulation for the anion-binding site located in the C-terminal extension, which is fully conserved in snake venom serine proteinases, that preferentially binds Cl1- instead of SO42-.

Produtores familiares e estratégias ligadas à terra

A manutenção e/ou a ampliação da terra compõem o eixo central em torno do qual os produtores familiares organizam sua vida e seu trabalho. Este artigo analisa as estratégias desses produtores em relação à divisão de herança e à sucessão, e as formas que utilizam para aquisição de novas áreas. O levantamento das características das famílias e da propriedade foi realizado por meio de um questionário aplicado junto a 89 produtores familiares de três municípios da mesorregião de São José do Rio Preto (SP). Posteriormente foi entrevistado um terço dos produtores de cada município que havia respondido ao questionário. A análise das estratégias fundiárias mostrou uma grande diversidade na forma de partilhar a herança e de conduzir a sucessão, sendo que ambos os processos são apoiados, basicamente, em regras tradicionais, embora mantenham uma fachada de adequação às normas legais. Quanto às estratégias de aquisição de mais terras, observou-se que os produtores são capazes de organizar complexas formas de capitalização, centradas em maiores esforços no trabalho e na contenção de gastos, além da utilização de políticas públicas favoráveis e de práticas costumeiras. Os arranjos intra-familiares e as formas de cooperação ligadas ao parentesco mais amplo também se mostraram importantes para a ampliação da propriedade.

Uma discussão do problema mente-corpo em Descartes e Espinosa, a partir da neurofilosofia de Antonio Damásio

Pós-graduação em Filosofia - FFC

Proposta para o uso e manejo sustentável da bacia hidrográfica do Ribeirão Guaratinguetá, SP

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Interdisciplinaridade e contextualização no novo ensino médio: conhecendo obstáculos e desafios no discurso dos professores de ciências

Nessa pesquisa discuto os desafios do novo ensino médio na ótica dos professores de ciências, sobretudo os que dizem respeito à proposta de ensino pautado na interdisciplinaridade e na contextualização. Para tanto, esse estudo foi desenvolvido tendo em vista responder como os professores estão lidando no contexto de suas práticas com os novos princípios do ensino médio e que desafios precisam ser enfrentados para a implementação da interdisciplinaridade e da contextualização no ensino, na percepção dos professores de ciências. Para abordar as questões norteadoras e atingir os objetivos propostos neste estudo, lancei mão da pesquisa documental, objetivando a leitura da legislação que deu suporte à refonna do ensino médio, e da pesquisa bibliográfica para abordar os conceitos centrais dessa pesquisa. Além disso, entrevistei professores das disciplinas Química, Física e Biologia através da entrevista estruturada. Os resultados da investigação evidenciaram relativo desconhecimento dos princípios da reforma preconizados nos documentos oficiais, pela maioria dos entrevistados. Entretanto, os professores não se mostraram alheios às discussões relacionadas à interdisciplinaridade e a contextualização, o que não significa que esses sujeitos revelem formas complexas de lidar com esses conceitos ou que implementem ações conscientemente elaboradas, tendo em vista o ensino interdisciplinar e contextualizado. Predomina, nas concepções dos professores, uma visão instrumental da interdisciplinaridade e da contextualização, em consonância com a concepção apresentada nos textos oficiais. Quanto aos desafios percebidos pelos professores para a implementação da interdisciplinaridade e da contextualização no ensino, estes ficaram circunscritos à sua dimensão contextual, isto é, os problemas estruturais da escola pública e os limites de espaço e tempo. A dimensão conceitual dos termos em questão, bem como os limites advindos da formação dos educadores, foram perifericamente problematizados.

Tenho feito/fiz a tese: uma proposta de caracterização do pretérito perfeito no Português

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

A magia em um texto técnico agronômico da antiguidade romana: o 'Opus agriculturae', de Paládio

This work analyses the chapter 35, book I, of the agricultural treatise Opus agriculturæ, written by Rutilius Taurus Aemilianus Palladius (V C.E.). In that chapter the author presents some recipes, called remedia, to protect the farm and the garden against weeds and weather phenomena, as blight and fogs. The magical practices are identified according to both the fundamental principles of magic (similarity, contiguity, contrariety), which rule magical thought, and some elements of magical symbology. As the author seems not to distinguish magic and science, for he brings together both kinds of recipes, the analysis of some remedia emphasizes a specific study on the materials and substances employed in those recipes and their value in Science today. This leads to the discussions of how magical thought works, what are the limits (if they actually exist) between Magic and Science and between Magic and Religion. This work covers the subjects above and it has the following pourposes: demonstrate the characteristics that authorize the remedia described by Palladius to be classified as folk magic; identify the relations between this kind of practice with more complex forms of magic, as with religion, with science; demonstrate the contribution of the folk magic in ancient Rome farming for the formulation of more apropriated criteria of evaluating magic in comparison to religious and scientific thought.

Use of shared memory in the context of embedded multi-core processors: exploration of the technology and its limits

Modern embedded systems embrace many-core shared-memory designs. Due to constrained power and area budgets, most of them feature software-managed scratchpad memories instead of data caches to increase the data locality. It is therefore programmers’ responsibility to explicitly manage the memory transfers, and this make programming these platform cumbersome. Moreover, complex modern applications must be adequately parallelized before they can the parallel potential of the platform into actual performance. To support this, programming languages were proposed, which work at a high level of abstraction, and rely on a runtime whose cost hinders performance, especially in embedded systems, where resources and power budget are constrained. This dissertation explores the applicability of the shared-memory paradigm on modern many-core systems, focusing on the ease-of-programming. It focuses on OpenMP, the de-facto standard for shared memory programming. In a first part, the cost of algorithms for synchronization and data partitioning are analyzed, and they are adapted to modern embedded many-cores. Then, the original design of an OpenMP runtime library is presented, which supports complex forms of parallelism such as multi-level and irregular parallelism. In the second part of the thesis, the focus is on heterogeneous systems, where hardware accelerators are coupled to (many-)cores to implement key functional kernels with orders-of-magnitude of speedup and energy efficiency compared to the “pure software” version. However, three main issues rise, namely i) platform design complexity, ii) architectural scalability and iii) programmability. To tackle them, a template for a generic hardware processing unit (HWPU) is proposed, which share the memory banks with cores, and the template for a scalable architecture is shown, which integrates them through the shared-memory system. Then, a full software stack and toolchain are developed to support platform design and to let programmers exploiting the accelerators of the platform. The OpenMP frontend is extended to interact with it.

1,2-Bis(2-benzimidazolyl)-1,2-ethanediol, a chiral, tridentate, facially coordinating ligand

The ligand 1,2-bis(1H-benzimidazol-2-yl)-1,2-ethanediol, 1, and its methylated derivative 2 are readily synthesized from tartaric acid, and act as chiral, facially coordinating tridentate ligands, forming complexes of composition ML2 with octahedral transition metals. The copper(II) complexes show distorted 4 + 2 coordination with benzimidazoles occupying the equatorial sites and alcohol functions weakly binding in the axial sites. Nickel(II) complexes in three different states of protonation show regular octahedral geometry with the alcohols mutually cis. Deprotonation of the coordinated alcohol produces little structural change but the monodeprotonated complex forms a hydrogen bonded dimer. Magnetic measurements show the hydrogen bonded bridge to offer a pathway for weak antiferromagnetic coupling. UV-Visible spectroscopy shows the ligand to have a field intermediate between water and pyridine. The diastereoselectivity of complexation depends on the geometry: nickel(II) shows a weak preference for the homochiral complex, whereas copper(II) forms almost exclusively homochiral complexes.

Geochemistry of basement clasts from sediment core CRP-3 in the ross Sea, Antarctica

Distribution patterns and petrographical and mineral chemistry data are described for the most representative basement lithologies occuring as clast in the c. 824 m thick Tertiary sedimentary sequence at the CRP-3 drillsite. These are granule to bolder grain size clasts of igneous and metamorphic rocks. Within the basement clast assemblage, granitoid pebbles are the predominant lithology. They consist of dominant grey biotic-bearing monzogranite, pink biotite-hornblende monzogranite, and biotite-bearing leucomomonzgranite. Minor lithologies include: actinolite-bearing leucotonalite, microgranite, biotite-hornblende quartz-monzonitic porphyr, and foliated biotic leucomonzogranite. Metamorphic clasts include rocks of both granitic and sedimentary derivation. They include mylonitic biotic orthogneiss, with or without garnet, muscovite-bearing quartzite, sillimanite-biotite paragneiss, biotite meta-sandstone, biotite-spotted schist, biotite-clacite-clinoamphibole meta-feldspathic arenite, biotite-calcite-clinozoisite meta-siltstone, biotite±clinoamphibole meta-marl, and graphite-bearing marble. As in previous CRP drillcores, the ubiquitous occurence of biotite±hornblende monzogranite pebbles is indicative of a local provenance, closely mirroring the dominance of these lithologies in the on-shore basement, where the Cambro-Ordovician Granite Harbour Intrusive Complex forms the most extensively exposed rock unit.