The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Antineoplastic Drugs as a Potential Risk Factor in Occupational Settings: Mechanisms of Action at the Cell Level, Genotoxic Effects, and Their Detection Using Different Biomarkers

U članku je prikazana osnovna podjela antineoplastičnih lijekova prema mehanizmima djelovanja na razini stanice. Objašnjeni su mehanizmi genotoksičnosti najvažnijih vrsta lijekova koji se primjenjuju u okviru uobičajenih protokola za liječenje zloćudnih novotvorina. Navedena je važeća klasifi kacija antineoplastika prema kancerogenom potencijalu, podaci o mutagenom potencijalu te je prikazana njihova podjela u skladu s anatomsko-terapijsko-kemijskim sustavom klasifi kacije. Sustavno su prikazani najvažniji rezultati svjetskih i hrvatskih istraživanja na populacijama radnika izloženih antineoplasticima, provedenih u razdoblju 1980.-2009. s pomoću četiri najčešće primjenjivane metode: analize izmjena sestrinskih kromatida, analize kromosomskih aberacija, mikronukleus-testa i komet-testa. Objašnjena su osnovna načela navedenih metoda te raspravljene njihove prednosti i nedostaci. Biološki pokazatelji daju važne podatke o individualnoj osjetljivosti profesionalno izloženih ispitanika koji mogu poslužiti unaprjeđenju postojećih uvjeta rada i upravljanju rizicima pri izloženosti genotoksičnim agensima. Na osnovi prednosti i nedostataka citogenetičkih metoda zaključeno je da je mikronukleus-test, koji podjednako uspješno dokazuje klastogene i aneugene učinke, jedna od najboljih metoda dostupnih za otkrivanje štetnih djelovanja antineoplastičnih lijekova koji su u aktivnoj primjeni.This article brings an overview of the mechanisms of action of antineoplastic drugs used in the clinical setting. It also describes the genotoxic potentials of the most important classes of antineoplastic drugs involved in standard chemotherapy protocols. Classifi cation of antineoplastic drugs according to the IARC monographs on the evaluation of carcinogenic risks to humans is accompanied by data on their mutagenicity and the most recent updates in the Anatomical Therapeutic Chemical (ATC) Classifi cation System. We report the main fi ndings of biomonitoring studies that were conducted in exposed healthcare workers all over the world between 1980 and 2009 using four biomarkers: sister chromatid exchanges, chromosome aberrations, micronuclei. and the comet assay. The methods are briefl y explained and their advantages and disadvantages discussed. Biomarkers provide important information on individual genome sensitivity, which eventually might help to improve current working practices and to manage the risks related with exposure to genotoxic agents. Taking into consideration all known advantages and drawbacks of the existing cytogenetic methods, the micronucleus assay, which is able to detect both clastogenic and aneugenic action, is the most suitable biomarker for assessing harmful effects of antineoplastic drugs currently used in health care

Pediatric lung MRI: Currently available and emerging techniques

OBJECTIVE. The purpose of this article is to review currently available and emerging techniques for pediatric lung MRI for general radiologists. CONCLUSION. MRI is a radiation-free alternative to CT, and clearly understanding the strengths and limitations of established and emerging techniques of pediatric lung MRI can allow practitioners to select and combine the optimal techniques, apply them in clinical practice, and potentially improve early diagnostic accuracy and patient management

Pediatric Lung MRI: Currently Available and Emerging Techniques

OBJECTIVE. The purpose of this article is to review currently available and emerging techniques for pediatric lung MRI for general radiologists. CONCLUSION. MRI is a radiation-free alternative to CT, and clearly understanding the strengths and limitations of established and emerging techniques of pediatric lung MRI can allow practitioners to select and combine the optimal techniques, apply them in clinical practice, and potentially improve early diagnostic accuracy and patient management

DDT domain is essential for Swi1’s functions.

<p>(A) Five-fold serial dilutions of the indicated cells were incubated on YES agar medium supplemented with the indicated drugs for 2 to 4 days at 32°C. Representative images of repeat experiments are shown. (B) Cells of indicated <i>swi1</i> mutants were engineered to express Rad22-YFP and grown in YES medium at 25°C until midlog phase. The percentages of nuclei with at least one Rad22-YFP focus are shown (left panel). At least 200 cells were counted for each strain. Error bars correspond to standard deviations obtained from at least three independent experiments. Quantification of Rad22-YFP foci according to the cell cycle stages was also performed by analyzing cell length, nuclei number and position, and the presence of a division plate, as described in our previous publications (right panel) <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0043988#pone.0043988-Noguchi1" target="_blank">[13]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0043988#pone.0043988-Noguchi2" target="_blank">[15]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0043988#pone.0043988-Ansbach1" target="_blank">[19]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0043988#pone.0043988-Noguchi4" target="_blank">[43]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0043988#pone.0043988-Noguchi6" target="_blank">[55]</a>. Schematic drawing for nuclear and morphological changes during the <i>S. pombe</i> cell cycle is shown (right panel). <i>swi1-h1</i> and <i>swi1</i>^Δ<i>DDT</i> cells displayed strong accumulation of Rad22-YFP foci during S and early G2 phases.</p