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Publications and source records attributed to Morales, J. C..
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The subthalamic nucleus (STN) is traditionally thought to restrict movement. Lesion or prolonged STN inhibition increases movement vigor and propensity, while optogenetic excitation typically has opposing effects. Subthalamic and motor activity are also inversely correlated in movement disorders. However, most STN neurons exhibit movement-related increases in firing. To address this paradox, STN activity was recorded and manipulated in head-fixed mice at rest and during self-initiated and -paced treadmill locomotion. The majority of STN neurons (type 1) exhibited locomotion-dependent increases in activity, with half encoding the locomotor cycle. A minority of neurons exhibited dips in activity or were uncorrelated with movement. Brief optogenetic inhibition of the dorsolateral STN (where type 1 neurons are concentrated) slowed and prematurely terminated locomotion. In Q175 Huntingtons disease mice abnormally brief, low-velocity locomotion was specifically associated with type 1 hypoactivity. Together these data argue that movement-related increases in STN activity contribute to optimal locomotor performance.
Herein, we present G4-iM Grinder as a system for potential G4, i-Motif and higher-order structure identification and characterization. Several grading tools of biological relevance and G4 in vitro formation probability are included in this highly modulable and robust engine. G4-iM Grinder improves other current quadruplex search engines when compared in capabilities and processing time. We used G4-iM Grinder in the analysis of the complete human genome whilst focusing on frequency and score of G-based structures. We studied the most recurrent potential quadruplex sequences (PQS) and the longest highest scoring potential higher order quadruplex sequences (PHOQS) in our genome. As proof of the analytical capabilities of G4-iM Grinder, we also analysed a new PHOQS and predicted the most probable PQS subunits to form it. Taking the human average PQS density as reference, we examined the genomes of organisms that cause leishmaniosis, diphtheria, brucellosis, meningitis, pneumonia, toxoplasmosis, tuberculosis, leprosy, AIDS, dengue fever and hepatitis C, and found they are very rich in PQS. G4-iM Grinder identified within many of these organisms several already known-to-form G4 sequences. Together, this suggests that G4-quadruplexes may potentially be important therapeutic targets against many of these organisms that currently kill millions worldwide. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=160 SRC="FIGDIR/small/532382v1_ufig1.gif" ALT="Figure 1"> View larger version (61K): org.highwire.dtl.DTLVardef@b01c08org.highwire.dtl.DTLVardef@56b3org.highwire.dtl.DTLVardef@3c1a63org.highwire.dtl.DTLVardef@1e88e04_HPS_FORMAT_FIGEXP M_FIG C_FIG