Does adult ADHD interact with COMT val 158 met genotype to influence working memory performance?

Peer reviewedPostprin

Microtubule depolymerization by the kinesin-8 motor Kip3p: a mathematical model

Proteins from the kinesin-8 family promote microtubule (MT) depolymerization, a process thought to be important for the control of microtubule length in living cells. In addition to this MT shortening activity, kinesin 8s are motors that show plus-end directed motility on MTs. Here we describe a simple model that incorporates directional motion and destabilization of the MT plus end by kinesin 8. Our model quantitatively reproduces the key features of length-vs-time traces for stabilized MTs in the presence of purified kinesin 8, including length-dependent depolymerization. Comparison of model predictions with experiments suggests that kinesin 8 depolymerizes processively, i.e., one motor can remove multiple tubulin dimers from a stabilized MT. Fluctuations in MT length as a function of time are related to depolymerization processivity. We have also determined the parameter regime in which the rate of MT depolymerization is length dependent: length-dependent depolymerization occurs only when MTs are sufficiently short; this crossover is sensitive to the bulk motor concentration.Comment: 34 pages, 11 figure

TIREOIDITE AGUDA

A tireoidite aguda (TA) é uma entidade rara entre as enfermidades da tireoide, porém sua incidência tem se elevado devido ao aumento do número de pacientes imunodeprimidos, bem como devido a anormalidades congênitas como fendas branquiais ou fístulas do seio piriforme, localizado entre a glândula tireoide e a hipofaringe. As infecções tireoidianas são patologias graves que merecem especial atenção em função de oferecer grande risco de complicação. Quando baseada em uma avaliação clínica rigorosa e capacitada, além de amparada por métodos diagnósticos por imagem e laboratoriais, seu desfecho é positivo. O objetivo deste trabalho é realizar uma revisão acerca da etiopatogenia, dos diagnósticos clínico e laboratorial e do tratamento da Tireoidite Supurativa Aguda.Palavras-chave: Tireoidite Supurativa Aguda. Abscesso Tireoidiano. Fístula do Seio Piriforme

Amine-Gold Linked Single-Molecule Junctions: Experiment and Theory

The measured conductance distribution for single molecule benzenediamine-gold junctions, based on 59,000 individual conductance traces recorded while breaking a gold point contact in solution, has a clear peak at 0.0064 G$_{0}$ with a width of $\pm$ 40%. Conductance calculations based on density functional theory (DFT) for 15 distinct junction geometries show a similar spread. Differences in local structure have a limited influence on conductance because the amine-Au bonding motif is well-defined and flexible. The average calculated conductance (0.046 G$_{0}$) is seven times larger than experiment, suggesting the importance of many-electron corrections beyond DFT

Measurement of the conductance of a hydrogen molecule

Recent years have shown steady progress in research towards molecular electronics [1,2], where molecules have been investigated as switches [3-5], diodes [6], and electronic mixers [7]. In much of the previous work a Scanning Tunnelling Microscope was employed to address an individual molecule. As this arrangement does not provide long-term stability, more recently metal-molecule-metal links have been made using break junction devices [8-10]. However, it has been difficult to establish unambiguously that a single molecule forms the contact [11]. Here, we show that a single H2 molecule can form a stable bridge between Pt electrodes. In contrast to results for other organic molecules, the bridge has a nearly perfect conductance of one quantum unit, carried by a single channel. The H2-bridge provides a simple test system and a fundamental step towards understanding transport properties of single-molecule devices.Comment: 6 pages, 4 figure

The Role of γ-Tubulin in Centrosomal Microtubule Organization

As part of a multi-subunit ring complex, γ-tubulin has been shown to promote microtubule nucleation both in vitro and in vivo, and the structural properties of the complex suggest that it also seals the minus ends of the polymers with a conical cap. Cells depleted of γ-tubulin, however, still display many microtubules that participate in mitotic spindle assembly, suggesting that γ-tubulin is not absolutely required for microtubule nucleation in vivo, and raising questions about the function of the minus end cap. Here, we assessed the role of γ-tubulin in centrosomal microtubule organisation using three-dimensional reconstructions of γ-tubulin-depleted C. elegans embryos. We found that microtubule minus-end capping and the PCM component SPD-5 are both essential for the proper placement of microtubules in the centrosome. Our results further suggest that γ-tubulin and SPD-5 limit microtubule polymerization within the centrosome core, and we propose a model for how abnormal microtubule organization at the centrosome could indirectly affect centriole structure and daughter centriole replication

Developing 3D SEM in a broad biological context

When electron microscopy (EM) was introduced in the 1930s it gave scientists their first look into the nanoworld of cells. Over the last 80 years EM has vastly increased our understanding of the complex cellular structures that underlie the diverse functions that cells need to maintain life. One drawback that has been difficult to overcome was the inherent lack of volume information, mainly due to the limit on the thickness of sections that could be viewed in a transmission electron microscope (TEM). For many years scientists struggled to achieve three-dimensional (3D) EM using serial section reconstructions, TEM tomography, and scanning EM (SEM) techniques such as freeze-fracture. Although each technique yielded some special information, they required a significant amount of time and specialist expertise to obtain even a very small 3D EM dataset. Almost 20 years ago scientists began to exploit SEMs to image blocks of embedded tissues and perform serial sectioning of these tissues inside the SEM chamber. Using first focused ion beams (FIB) and subsequently robotic ultramicrotomes (serial block-face, SBF-SEM) microscopists were able to collect large volumes of 3D EM information at resolutions that could address many important biological questions, and do so in an efficient manner. We present here some examples of 3D EM taken from the many diverse specimens that have been imaged in our core facility. We propose that the next major step forward will be to efficiently correlate functional information obtained using light microscopy (LM) with 3D EM datasets to more completely investigate the important links between cell structures and their functions. Lay Description Life happens in three dimensions. For many years, first light, and then EM struggled to image the smallest parts of cells in 3D. With recent advances in technology and corresponding improvements in computing, scientists can now see the 3D world of the cell at the nanoscale. In this paper we present the results of high resolution 3D imaging in a number of diverse cells and tissues from multiple species. 3D reconstructions of cell structures often revealed them to be significantly more complex when compared to extrapolations made from 2D studies. Correlating functional 3D LM studies with 3D EM results opens up the possibility of making new strides in our understanding of how cell structure is connected to cell function

A doublecortin containing microtubule-associated protein is implicated in mechanotransduction in Drosophila sensory cilia

Mechanoreceptors are sensory cells that transduce mechanical stimuli into electrical signals and mediate the perception of sound, touch and acceleration. Ciliated mechanoreceptors possess an elaborate microtubule cytoskeleton that facilitates the coupling of external forces to the transduction apparatus. In a screen for genes preferentially expressed in Drosophila campaniform mechanoreceptors, we identified DCX-EMAP, a unique member of the EMAP family (echinoderm–microtubule-associated proteins) that contains two doublecortin domains. DCX-EMAP localizes to the tubular body in campaniform receptors and to the ciliary dilation in chordotonal mechanoreceptors in Johnston's organ, the fly's auditory organ. Adult flies carrying a piggyBac insertion in the DCX-EMAP gene are uncoordinated and deaf and display loss of mechanosensory transduction and amplification. Electron microscopy of mutant sensilla reveals loss of electron-dense materials within the microtubule cytoskeleton in the tubular body and ciliary dilation. Our results establish a catalogue of candidate genes for Drosophila mechanosensation and show that one candidate, DCX-EMAP, is likely to be required for mechanosensory transduction and amplification