scholarly journals Genomic normalization for sequencing libraries enrichment for rare somatic retroelement insertions

2018 ◽  
Author(s):  
Alexander Komkov ◽  
Gaiaz Nugmanov ◽  
Maria Salutina ◽  
Anastasia Minervina ◽  
Konstantin Khodosevich ◽  
...  

AbstractBackgroundThere is increasing evidence that the transpositional activity of retroelements (REs) is not limited to germ line cells, but often occurs in tumor and normal somatic cells. Somatic transpositions were found in several human tissues and are especially typical for the brain. Several computational and experimental approaches for detection of somatic retroelement insertions was developed in the past few years. These approaches were successfully applied to detect somatic insertions in clonally expanded tumor cells. At the same time, identification of somatic insertions presented in small proportion of cells, such as neurons, remains a considerable challenge.ResultsIn this study, we developed a normalization procedure for library enrichment by DNA sequences corresponding to rare somatic RE insertions. Two rounds of normalization increased the number of fragments adjacent to somatic REs in the sequenced sample by more than 26-fold, and the number of identified somatic REs was increased by 7.9-fold.ConclusionsThe developed technique can be used in combination with vast majority of modern RE identification approaches and can dramatically increase their capacity to detect rare somatic RE insertions in different types of cells.

Author(s):  
U. Aebi ◽  
P. Rew ◽  
T.-T. Sun

Various types of intermediate-sized (10-nm) filaments have been found and described in many different cell types during the past few years. Despite the differences in the chemical composition among the different types of filaments, they all yield common structural features: they are usually up to several microns long and have a diameter of 7 to 10 nm; there is evidence that they are made of several 2 to 3.5 nm wide protofilaments which are helically wound around each other; the secondary structure of the polypeptides constituting the filaments is rich in ∞-helix. However a detailed description of their structural organization is lacking to date.


Author(s):  
C. N. Sun ◽  
C. Araoz ◽  
H. J. White

The ultrastructure of a cerebral primitive neuroectodermal tumor has been reported previously. In the present case, we will present some unusual previously unreported membranous structures and alterations in the cytoplasm and nucleus of the tumor cells.Specimens were cut into small pieces about 1 mm3 and immediately fixed in 4% glutaraldehyde in phosphate buffer for two hours, then post-fixed in 1% buffered osmium tetroxide for one hour. After dehydration, tissues were embedded in Epon 812. Thin sections were stained with uranyl acetate and lead citrate.In the cytoplasm of the tumor cells, we found paired cisternae (Fig. 1) and annulate lamellae (Fig. 2) noting that the annulate lamellae were sometimes associated with the outer nuclear envelope (Fig. 3). These membranous structures have been reported in other tumor cells. In our case, mitochondrial to nuclear envelope fusions were often noted (Fig. 4). Although this phenomenon was reported in an oncocytoma, their frequency in the present study is quite striking.


2017 ◽  
Vol 2 (15) ◽  
pp. 9-23 ◽  
Author(s):  
Chorong Oh ◽  
Leonard LaPointe

Dementia is a condition caused by and associated with separate physical changes in the brain. The signs and symptoms of dementia are very similar across the diverse types, and it is difficult to diagnose the category by behavioral symptoms alone. Diagnostic criteria have relied on a constellation of signs and symptoms, but it is critical to understand the neuroanatomical differences among the dementias for a more precise diagnosis and subsequent management. With this regard, this review aims to explore the neuroanatomical aspects of dementia to better understand the nature of distinctive subtypes, signs, and symptoms. This is a review of English language literature published from 1996 to the present day of peer-reviewed academic and medical journal articles that report on older people with dementia. This review examines typical neuroanatomical aspects of dementia and reinforces the importance of a thorough understanding of the neuroanatomical characteristics of the different types of dementia and the differential diagnosis of them.


2010 ◽  
Vol 24 (4) ◽  
pp. 249-252 ◽  
Author(s):  
Márk Molnár ◽  
Roland Boha ◽  
Balázs Czigler ◽  
Zsófia Anna Gaál

This review surveys relevant and recent data of the pertinent literature regarding the acute effect of alcohol on various kinds of memory processes with special emphasis on working memory. The characteristics of different types of long-term memory (LTM) and short-term memory (STM) processes are summarized with an attempt to relate these to various structures in the brain. LTM is typically impaired by chronic alcohol intake but according to some data a single dose of ethanol may have long lasting effects if administered at a critically important age. The most commonly seen deleterious acute effect of alcohol to STM appears following large doses of ethanol in conditions of “binge drinking” causing the “blackout” phenomenon. However, with the application of various techniques and well-structured behavioral paradigms it is possible to detect, albeit occasionally, subtle changes of cognitive processes even as a result of a low dose of alcohol. These data may be important for the consideration of legal consequences of low-dose ethanol intake in conditions such as driving, etc.


Author(s):  
Olga Lemzyakova

Refraction of the eye means its ability to bend (refract) light in its own optical system. In a normal state, which is called emmetropia, light rays passing through the optical system of the eye focus on the retina, from where the impulse is transmitted to the visual cortex of the brain and is analyzed there. A person sees equally well both in the distance and near in this situation. However, very often, refractive errors develop as a result of various types of influences. Myopia, or short-sightedness, occurs when the light rays are focused in front of the retina as a result of passing through the optical system of the eye. In this case, a person will clearly distinguish close objects and have difficulties in seeing distant objects. On the opposite side is development of farsightedness (hypermetropia), in which the focusing of light rays occurs behind the retina — such a person sees distant objects clearly, but outlines of closer objects are out of focus. Near vision impairment in old age is a natural process called presbyopia, it develops due to the lens thickening. Both myopia and hypermetropia can have different degrees of severity. The variant, when different refractive errors are observed in different eyes, is called anisometropia. In the same case, if different types of refraction are observed in the same eye, it is astigmatism, and most often it is a congenital pathology. Almost all of the above mentioned refractive errors require correction with spectacles or use of contact lenses. Recently, people are increasingly resorting to the methods of surgical vision correction.


2008 ◽  
Vol 59 (7) ◽  
Author(s):  
Corina Samoila ◽  
Alfa Xenia Lupea ◽  
Andrei Anghel ◽  
Marilena Motoc ◽  
Gabriela Otiman ◽  
...  

Denaturing High Performance Liquid Chromatography (DHPLC) is a relatively new method used for screening DNA sequences, characterized by high capacity to detect mutations/polymorphisms. This study is focused on the Transgenomic WAVETM DNA Fragment Analysis (based on DHPLC separation method) of a 485 bp fragment from human EC-SOD gene promoter in order to detect single nucleotide polymorphism (SNPs) associated with atherosclerosis and risk factors of cardiovascular disease. The fragment of interest was amplified by PCR reaction and analyzed by DHPLC in 100 healthy subjects and 70 patients characterized by atheroma. No different melting profiles were detected for the analyzed DNA samples. A combination of computational methods was used to predict putative transcription factors in the fragment of interest. Several putative transcription factors binding sites from the Ets-1 oncogene family: ETS member Elk-1, polyomavirus enhancer activator-3 (PEA3), protein C-Ets-1 (Ets-1), GABP: GA binding protein (GABP), Spi-1 and Spi-B/PU.1 related transcription factors, from the Krueppel-like family: Gut-enriched Krueppel-like factor (GKLF), Erythroid Krueppel-like factor (EKLF), Basic Krueppel-like factor (BKLF), GC box and myeloid zinc finger protein MZF-1 were identified in the evolutionary conserved regions. The bioinformatics results need to be investigated further in others studies by experimental approaches.


2018 ◽  
Vol 25 (9) ◽  
pp. 1073-1089 ◽  
Author(s):  
Santiago Vilar ◽  
Eduardo Sobarzo-Sanchez ◽  
Lourdes Santana ◽  
Eugenio Uriarte

Background: Blood-brain barrier transport is an important process to be considered in drug candidates. The blood-brain barrier protects the brain from toxicological agents and, therefore, also establishes a restrictive mechanism for the delivery of drugs into the brain. Although there are different and complex mechanisms implicated in drug transport, in this review we focused on the prediction of passive diffusion through the blood-brain barrier. Methods: We elaborated on ligand-based and structure-based models that have been described to predict the blood-brain barrier permeability. Results: Multiple 2D and 3D QSPR/QSAR models and integrative approaches have been published to establish quantitative and qualitative relationships with the blood-brain barrier permeability. We explained different types of descriptors that correlate with passive diffusion along with data analysis methods. Moreover, we discussed the applicability of other types of molecular structure-based simulations, such as molecular dynamics, and their implications in the prediction of passive diffusion. Challenges and limitations of experimental measurements of permeability and in silico predictive methods were also described. Conclusion: Improvements in the prediction of blood-brain barrier permeability from different types of in silico models are crucial to optimize the process of Central Nervous System drug discovery and development.


2020 ◽  
Vol 20 (9) ◽  
pp. 800-811 ◽  
Author(s):  
Ferath Kherif ◽  
Sandrine Muller

In the past decades, neuroscientists and clinicians have collected a considerable amount of data and drastically increased our knowledge about the mapping of language in the brain. The emerging picture from the accumulated knowledge is that there are complex and combinatorial relationships between language functions and anatomical brain regions. Understanding the underlying principles of this complex mapping is of paramount importance for the identification of the brain signature of language and Neuro-Clinical signatures that explain language impairments and predict language recovery after stroke. We review recent attempts to addresses this question of language-brain mapping. We introduce the different concepts of mapping (from diffeomorphic one-to-one mapping to many-to-many mapping). We build those different forms of mapping to derive a theoretical framework where the current principles of brain architectures including redundancy, degeneracy, pluri-potentiality and bow-tie network are described.


Author(s):  
Gordon Moore ◽  
John A. Quelch ◽  
Emily Boudreau

Chapter 2 asks the critical question of whether healthcare is different from other consumer-driven markets. In the past, many pushed back on the notion that healthcare could be a consumer-driven industry, arguing that it is fundamentally different from other markets. This chapter acknowledges and reviews these critiques, highlighting four areas that might present challenges to increasing consumer choice in healthcare: the special relationship between doctor and patient, ethics and morality, individual choice versus collective benefit, and the health consequences of consumer choice. In doing so, this chapter also presents a schematic for thinking about the different types of healthcare choices, arguing that not all choices are equal and consumers may be more prepared to make decisions in some areas as opposed to others. In presenting the counterargument to consumer choice, this chapter asks the reader to consider the drawbacks and potential limitations of consumer choice in healthcare.


Author(s):  
Patricia Pelley

This chapter demonstrates how the process of decolonization and the ensuing separation of Vietnam into a northern and southern state as part of the Cold War in Asia led to different types of history-writing. In both Vietnamese regimes, the writing of history had to serve the state, and in both countries historians emphasized its political function. Whereas North Vietnam located itself in an East Asian and Marxist context, historians of South Vietnam positioned it within a Southeast Asian setting and took a determinedly anti-communist position. After 1986—over a decade after reunification—with past tensions now relaxed, the past could be revaluated more openly under a reformist Vietnamese government that now also permitted much greater interaction with foreign historians.


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