Mining the pharmacogenomics literature--a survey of the state of the art

This article surveys efforts on text mining of the pharmacogenomics literature, mainly from the period 2008 to 2011. Pharmacogenomics (or pharmacogenetics) is the field that studies how human genetic variation impacts drug response. Therefore, publications span the intersection of research in genotypes, phenotypes and pharmacology, a topic that has increasingly become a focus of active research in recent years. This survey covers efforts dealing with the automatic recognition of relevant named entities (e.g. genes, gene variants and proteins, diseases and other pathological phenomena, drugs and other chemicals relevant for medical treatment), as well as various forms of relations between them. A wide range of text genres is considered, such as scientific publications (abstracts, as well as full texts), patent texts and clinical narratives. We also discuss infrastructure and resources needed for advanced text analytics, e.g. document corpora annotated with corresponding semantic metadata (gold standards and training data), biomedical terminologies and ontologies providing domain-specific background knowledge at different levels of formality and specificity, software architectures for building complex and scalable text analytics pipelines and Web services grounded to them, as well as comprehensive ways to disseminate and interact with the typically huge amounts of semiformal knowledge structures extracted by text mining tools. Finally, we consider some of the novel applications that have already been developed in the field of pharmacogenomic text mining and point out perspectives for future research.     

Histochemical investigations on the localization of the purple acid phosphatase in the bovine spleen

Summary The localization of the purple tartrate-resistant, iron-containing acid phosphatase in the bovine spleen was studied by enzyme histochemistry at the light and electron microscopic levels as well as by immunohistochemistry. The purple phosphatase was localized only in lysosome-like organelles of cells belonging to the reticulo-phagocytic system. The same cells were identified as containing large iron(III)-deposits as ferritin in homogeneously granular accumulations and freely in the cytoplasm, or as hemosiderin in siderosomes. The phagocytosing cells containing purple phosphatase and ferritin often had close contact with clusters of aged and deformed erythrocytes.A possible catabolic role of the purple enzyme as a phosphatase degrading phosphoproteins of the erythrocyte membrane and the cytoskeleton was assumed.     

Histochemical investigations on the localization of the purple acid phosphatase in the bovine spleen

The localization of the purple tartrate-resistant, iron-containing acid phosphatase in the bovine spleen was studied by enzyme histochemistry at the light and electron microscopic levels as well as by immunohistochemistry. The purple phosphatase was localized only in lysosome-like-organelles of cells belonging to the reticulo-phagocytic system. The same cells were identified as containing large iron(III)-deposits as ferritin in homogeneously granular accumulations and freely in the cytoplasm, or as hemosiderin in siderosomes. The phagocytosing cells containing purple phosphatase and ferritin often had close contact with clusters of aged and deformed erythrocytes. A possible catabolic role of the purple enzyme as a phosphatase degrading phosphoproteins of the erythrocyte membrane and the cytoskeleton was assumed.     

Theoretical study of the optimal shape of the front profile of the lens in the eye of the scallop,Pecten

The optimal shape of the front profile of the thick lens in the eye of the scallop,Pecten is theoretically, geometric optically investigated as a function of the refractive index of the lens and the retina, as well as of the geometrical parameters of the eye. The shape of the theoretical front surfaces is compared with that of the real, experimentally determined front face of the lens. The degree of correction of the lens for spherical aberration of the reflecting spherical mirror in thePecten eye is examined. The optimal shape of the front profile of the lens depends strongly on a set of parameters, such that a certain fine tuning is required among them to assure a full correction for spherical aberration. The extreme variability of the eye parameters and the shape of the front face of the lens in the scallop is inconsistent with this fine tuning requirement. The degree of correction of thePecten lens for spherical aberration might not be as good as it could be, a possible biooptical reason for which is discussed.     

食草动物与植物的相互关系

动植物相互作用是决定动植物群落结构的重要因素[50 ] 。动物从多方面和多层次影响植物 ,最后都反映到植物群落结构的变化。而变化的植物群落又从各方面影响动物的生理、行为、种群特征、分布、种间关系等方面 ,最终反映到动物群落水平层次的改变 ,所以对动物群落与植物群落关系及机理的研究是个内容十分丰富的重要领域。1　食草动物的牧食作用对植物的影响食草动物的牧食作用 ,常使植物形态和结构发生变化 ,如导致植株的“矮化”或“匍匐化”,增加剌结构和机械结构 ,以抵御进一步被牧食[42 ] 。一定强度的牧食会加速植物光合作用强度 ,从而…     

Histochemical studies on the lipids in the epithelium of the fetal colon

Summary Large intestines from 30 fetuses with crown-rump lengths ranging from 26 to 180 mm have been studied histochemically as to their epithelial content of lipids. These lipids have been localized intracellularly and basally in the cells, and comparative studies of the colon and the small intestine have demonstrated that there are considerable amounts of lipids in the colon as compared with the small intestine.It is concluded that the main part of the lipids consist of saturated and unsaturated constituents.The possible explanations of the lipids as absorbed material, biological active material synthetized de novo or as material involved in the metabolism of fetal surface cells are discussed.This work was supported by a grant from the Aid of the Crippled Children, New York.     

Aptychi: the myth of the ammonite operculum

Re-examination of ammonite specimens with the aptychus apparently in place closing the aperture has shown that these are accidents of preservation and have been misinterpreted as indicating that aptychi functioned as opercula. There remain no convincing grounds for doubting that aptychi functioned only as lower jaws of ammonites, not as opercula. Chance preservation of exceptional specimens can sometimes be misleading. Ammonoidea, aptychi, anoptychi, functional morphology .     

Senescence: the good the bad and the dysfunctional

Nearly 50 years have elapsed since Hayflick challenged the dogma that individual human cells were immortal by demonstrating that after a predictable number of cellular divisions, normal human fibroblasts eventually entered a state of permanent growth arrest [Hayflick L: The limited in vitro lifetime of human diploid cell strains. Exp Cell Res 1965, 37:614-636.; Hayflick L, Moorhead PS: The serial cultivation of human diploid cell strains. Exp Cell Res 1961, 25:585-621]. This growth arrest, referred to as senescence, was hypothesized to function as a tumor suppressive mechanism, capable of limiting the replicative capacity of an incipient tumor cell. While originally met with skepticism, the existence of senescence and its importance as a tumor suppressive mechanism is now accepted. Here, we highlight this work and introduce studies that indicate that while senescent cells themselves cannot produce a neoplasia, they possess the ability to promote the growth of nearby preneoplastic cells and in this way may contribute to age-related increases in tumor incidences. This added level of complexity suggests that senescence functions as a biological 'double edged sword.'     

Cytochemical study of the DNA and histone in the tissues of the lily anther in the course of microsporo- and gametogenesis]

The DNA and histone content in the microsporocytes, microspores, generative and vegetative cells of the pollen grain of Lilium candidum L., as well as in the anther wall tissues, was estimated by double wavelength cytophotometry. The lack of histone, as compared with DNA content, was demonstrated in the microsporocytes at the late premeiotic interphase and early meiotic prophase, as well as in the young microspores and anther wall tissues. The analysis of hydrolysis curves suggests the increase of non-condensed chromatin during endothelial cell differentiation.     

Role of the thyroid in the involution of the mesonephric Malpighian corpuscles in the chick embryo

The mesonephros of the chick embryo normally begins to regress during the second half of embryonic life. Experimental methods, such as adenohypophysis grafting, hypophysectomy or use of antithyroid drugs, which stimulate or depress the thyroid function of the embryo, modified accordingly the regressive processes occurring in the mesonephric Malpighian corpuscles, particularly at the level of the glomerular basement laminae. These results as well as the known sensitivity of the mesonephros to thyroxine and the concordance between the steps of embryonic thyroid development and the mesonephric modifications show that the thyroid normally plays a major determining role in this phenomenon.     

Structure of the mammillary bodies of the hypothalamus of the bottlenosed dolphin

In the bottlenosed dolphin (Tursiops truncatus) the hypothalamic corpus mammillaris has been studied using interperpendicular, sagittal, frontal and horizontal serial sections, impregnated in silver and stained with cresil-violet. Comparatively small dimentions of the corpora mammillaria in the bottlenosed dolphin are explained by presence of only two nuclei, medial and lateral. The lateral nucleus is nearly three times as large as the medial one. The size of the neurons in the medial nucleus is on the average two times as large as that of neurons in the lateral nucleus. The density of the neural cells distribution is a little greater in the lateral nucleus. The structure of the bottlenosed dolphin corpora mammillaria is compared with similar structures in other animals and the human being.     

Effect of reserpine on the differentiation of the external granular layer of the cerebellum in the chick embryo

In this work we analyse the effect produced by reserpine on the development of thickness and cell number in the external granular layer in the cerebellum of chick embryo. A striking 48-hour histogenetic delay is observed in the treated embryos relative to controls, as show by greater thickness and cell density of this layer in the former, as well as by retarded appearance of a typical radial morphological organization of the external granular layer.     

Evidence that the voltage-dependent component in the fertilization process is contributed by the sperm

To investigate the mechanisms that account for the voltage dependence of fertilization and provide an electrical block to polyspermy, we studied cross-fertilizations between three species of amphibians having different degrees of voltage dependence. Anurans, such as the toad Bufo japonicus, as well as the primitive urodele Hynobius nebulosus, have voltage-dependent fertilization; other urodeles, such as Cynops pyrrhogaster, have voltage-independent fertilization (Y. Iwao, 1989, Dev. Biol. 134, 438-445). Entry of Hynobius sperm into Cynops eggs was blocked by clamping the egg's membrane potential at +40 mV, as is the case for fertilization of Hynobius eggs with Hynobius sperm, but not for fertilization of Cynops eggs with Cynops sperm. Therefore, fertilization was voltage dependent in an experimental condition where only the sperm could be contributing this characteristic. The voltage-dependent properties of fertilization between Bufo eggs and Hynobius sperm were also characteristic of the sperm species; fertilization was blocked at +50 mV as in Hynobius fertilization, but not at +20 mV as in Bufo fertilization. These results support the conclusion that the voltage dependence of fertilization results from a component contributed by the sperm.     

On the role of the pineal in thermoregulation in the pigeon

Diurnal rhythm in body temperature of pigeons subjected to different experimental conditions (pinealectomized, sham-operated, melatonin-implanted, cold-exposed) was studied under a 12 h light and 12 h dark regimen. The body temperature of pigeons during photophase was higher than that during scotophase in the normal as well as every treatment group studied. Pinealectomized pigeons showed higher body temperature in the photophase as well as scotophase, than that of the normal and sham-operated birds when examined 2 or 3 weeks following the post-surgical acclimatization to 25 or 3 degrees C. However, subcutaneous implantation of melatonin pellets into pinealectomized pigeons nullified or even reversed the hyperthermic effect of pinealectomy. Exposure of pigeons to--18 degrees C for 280 min during photophase as well as scotophase, produced a marked drop in body temperature in pinealectomized, sham-operated and normal pigeons. The pinealectomized pigeons exhibited a higher body temperature than that of the sham-operated and normal ones when exposed to--18 degrees C during the photophase, but not during the scotophase. It was concluded that while the pineal is not necessary for maintaining the daily thermal rhythm in the avian body, it has a thermoregulatory role, in that it prevents rise in body temperature in warm (25 degrees C) acclimatized and chronic cold (3 degrees C) exposed birds. In acute short-term cold (--18 degrees C) exposure however, the temperature regulatory role of the pineal was not effective during the scotophase.     

Forming of the visual cognitive structures in the monkey conditioned-reflex behaviour: the dependence on the sensory information

In monkeys, changes in size and shape of figures led to a significant decrease of correct solutions in training and a considerable increase of refusals from solution of tasks as well as the time of their motor response. The invariance of differentiation in this case was achieved after additional training. The data obtained show that, based on the stimulus sensory processing in conditioned-reflex training, in the long-term memory some differentiating signs are formed: the cognitive structures (the functional neurophysiological mechanisms) maintaining the classification of visual images. With these structures, temporary conditioned connection will be established. Their formation will be determined by the type of sensory information and provided for by existence in the long-term memory of separate subsystems for spatial as well as non-spatial information.     

Sensing the fat: fatty acid metabolism in the hypothalamus and the melanocortin system

Recent evidence has demonstrated that circulating long chain fatty acids act as nutrient abundance signals in the hypothalamus. Moreover, pharmacological inhibition of fatty acid synthase (FAS) results in profound decrease in food intake and body weight in rodents. These anorectic actions are mediated by the modulation of hypothalamic neuropeptide systems, such as melanocortins. In this review, we summarize what is known about lipid sensing and fatty acid metabolism in the hypothalamus. Understanding these molecular mechanisms could provide new pharmacological targets for the treatment of obesity and appetite disorders, as well as novel concepts in the nutritional design.     

Perihemorheology: the bridge between the vessel-blood organ and the organs it penetrates

Perihemorheology concerns the rheology of fluids and structures in the perivascular spaces. Furthermore, the term refers to the exchanges of rheological processes between the vessel-blood organ and its surrounding tissues, as well as in reverse. In 1960, the vessel wall and the circulating blood were considered by the author as an entity which in 1981 he postulated as an organ, named the 'vessel-blood organ', penetrating all other organs. This communication is not a survey but is intended to stimulate biomedical thinking regarding the importance of perihemorheology. The significance of the endoendothelial fibrin(ogenin) lining (EEFL) and fibrin(ogenin) as constituent of the interendothelial cement and the basement membrane in relation to perihemorheology is stressed. The role of albumin in the exchanges between hemorheology and perihemorheology is discussed. The protein content, as found by Witte, in the perivascular spaces as compared to the blood is emphasized regarding the importance of interrelations between the vessel-blood organ and rheological processes in the perivascular spaces. Recent studies, particularly by Laurent and his group, pertaining to hyaluronan in perivascular spaces and the blood demonstrate also the importance of the interrelationship between hemorheology and perihemorheology. The term 'blood-brain barrier', considered no longer to be adequate, is replaced by the term 'basement membrane-brain barrier'. It is proposed that the basement membrane of the vessel-blood organ penetrating the brain may contain certain constituents, unknown thus far, and may have a different structure from the basement membrane of the vessel-blood organ penetrating organs other than the brain.     

The effect of distension of the left ventricle of the heart on the length of the individual myocardial fibers

Based on the ellipsoid model of the left ventricle and the helicoidal course of the left ventricular myocardial fibers, a theory has been developed for calculating the length of the individual myocardial fibers. Numerical solutions of the final equation show that when the left ventricle is distended, the increase in length of the myocardial fibers is not uniform throughout the thickness of the myocardial wall. It was shown that with increasing dimensions of the left ventricle, the distension of the myocardial fibers becomes smaller as one advances from the endocardium to the middle layer of fibers, whereas it increases as one advances from the middle layer to the epicardial layer. The mechanism by which this effect is brought about as well as its physiological implications are discussed.     

Health status of the stands and the young growth in the native spruce forests at the ural foothills,the upper reaches of the Pechora River

Health status of trees was studied in five types of native spruce forests in the Pechora-Ilych Nature Biosphere Reserve. The study has shown that trees in the old-growth bilberry-spruce and fern-shamrock-spruce forests can be characterized as “healthy”, with damage index varying from 0.03 to 0.5. The haircap-moss spruce forest with damage index 0.7 is categorized as a “weakened stand”. Regeneration was pronounced in all forest types. Young growth (1500 to 4300 stems/ha) is mainly composed of conifers and is classified as “healthy”.     

On the challenges of the HapMap resource

The International HapMap Project provides a key resource of genotypic data on human lymphoblastoid cell lines derived from four major world populations of European, African, Chinese and Japanese ancestry for researchers to associate with various phenotypic data to find genes affecting health, disease and response to drugs. Recently, the HapMap resource has significantly benefited research areas such as gene expression variation studies. Besides some intrinsic limitations, there are a few challenges that should be considered in the next wave of research using this tremendous resource. We suggest that overcoming these challenges or considering the confounding variables in the interpretation of results can provide more insights into the current views of the human genome as well as complex traits such as drug response variation and susceptibility to common diseases.