The timing database: An open-access, live repository for interval timing studies.

Interval timing refers to the ability to perceive and remember intervals in the seconds to minutes range. Our contemporary understanding of interval timing is derived from relatively small-scale, isolated studies that investigate a limited range of intervals with a small sample size, usually based on a single task. Consequently, the conclusions drawn from individual studies are not readily generalizable to other tasks, conditions, and task parameters.

Temporal scaling and computing time in neural circuits: Should we stop watching the clock and look for its gears?

Timing underlies a variety of functions, from walking to perceiving causality. Neural timing models typically fall into one of two categories-"ramping" and "population-clock" theories. According to ramping models, individual neurons track time by gradually increasing or decreasing their activity as an event approaches.

A limited cerebellar contribution to suprasecond timing across differing task demands.

The involvement of the cerebellum in suprasecond interval timing (i.e., timing in the seconds to minutes range) is controversial.

The dorsal hippocampus' role in context-based timing in rodents.

To act proactively, we must predict when future events will occur. Individuals generate temporal predictions using cues that indicate an event will happen after a certain duration elapses. Neural models of timing focus on how the brain represents these cue-duration associations.

Nonhuman sequence learning findings argue against Hoerl and McCormack's two systems of temporal cognition.

Hoerl & McCormack propose that animals learn sequences through an entrainment-like process, rather than tracking the temporal addresses of each event in a given sequence. However, past research suggests that animals form "temporal maps" of sequential events and also comprehend the concept of ordinal position. These findings suggest that a clarification or qualification of the authors' hypothesis is needed.

Cerebellar D1DR-expressing neurons modulate the frontal cortex during timing tasks.

Converging lines of evidence suggest that the cerebellum plays an integral role in cognitive function through its interactions with association cortices like the medial frontal cortex (MFC). It is unknown precisely how the cerebellum influences the frontal cortex and what type of information is reciprocally relayed between these two regions. A subset of neurons in the cerebellar dentate nuclei, or the homologous lateral cerebellar nuclei (LCN) in rodents, express D1 dopamine receptors (D1DRs) and may play a role in cognitive processes.

Cerebellar Theta Frequency Transcranial Pulsed Stimulation Increases Frontal Theta Oscillations in Patients with Schizophrenia.

Cognitive dysfunction is a pervasive and disabling aspect of schizophrenia without adequate treatments. A recognized correlate to cognitive dysfunction in schizophrenia is attenuated frontal theta oscillations. Neuromodulation to normalize these frontal rhythms represents a potential novel therapeutic strategy.

Recalibrating timing behavior via expected covariance between temporal cues.

Individuals must predict future events to proactively guide their behavior. Predicting when events will occur is a critical component of these expectations. Temporal expectations are often generated based on individual cue-duration relationships.

Striatal dopamine and the temporal control of behavior.

Striatal dopamine strongly regulates how individuals use time to guide behavior. Dopamine acts on D1- and D2- dopamine receptors in the striatum. However, the relative role of these receptors in the temporal control of behavior is unclear.

Attenuation of cocaine seeking in rats via enhancement of infralimbic cortical activity using stable step-function opsins.

Rationale: The infralimbic cortex (IL) and its downstream projection target the nucleus accumbens shell (NAshell) mediate the active suppression of cocaine-seeking behavior. Although an optogenetic approach would be beneficial for stimulating the IL and its efferents to study their role during reinstatement of cocaine seeking, the use of channelrhodopsin introduces significant difficulties, as optimal stimulation parameters are not known.

Objectives: The present experiments utilized a stable step-function opsin (SSFO) to potentiate endogenous activity in the IL and in IL terminals in the NAshell during cocaine-seeking tests to determine how these manipulations affect cocaine-seeking behaviors.

Amygdala central nucleus modulation of cerebellar learning with a visual conditioned stimulus.

Previous studies found that reversible inactivation of the central amygdala (CeA) severely impairs acquisition and retention of cerebellum-dependent eye-blink conditioning (EBC) with an auditory conditioned stimulus (CS). A monosynaptic pathway between the CeA and basilar pontine nuclei (BPN) may be capable of facilitating cerebellar learning. However, given that the CeA projects to the medial auditory thalamus, a critical part of the auditory CS pathway in EBC, the CeA influence on cerebellar learning could be specific to auditory stimuli.

Non-cortical magnitude coding of space and time by pigeons.

Considerable research in cognitive science, neuroscience, and developmental science has revealed that the temporal, spatial, and numerical features of a stimulus can interact with one another [1,2], as when larger stimuli are perceived as lasting longer than smaller stimuli. These findings have inspired the prominent hypothesis that time, space, and number are processed by a 'common magnitude system', which represents these dimensions via the same unit of magnitude [3,4]. According to current theorizing, the parietal cortex mediates this system [4].

Rodent Medial Frontal Control of Temporal Processing in the Dorsomedial Striatum.

Although frontostriatal circuits are critical for the temporal control of action, how time is encoded in frontostriatal circuits is unknown. We recorded from frontal and striatal neurons while rats engaged in interval timing, an elementary cognitive function that engages both areas. We report four main results.

Optogenetic Stimulation of Frontal D1 Neurons Compensates for Impaired Temporal Control of Action in Dopamine-Depleted Mice.

Disrupted mesocortical dopamine contributes to cognitive symptoms of Parkinson's disease (PD). Past work has implicated medial frontal neurons expressing D1 dopamine receptors (D1DRs) in temporal processing. Here, we investigated whether these neurons can compensate for behavioral deficits resulting from midbrain dopamine dysfunction.

Interval timing, temporal averaging, and cue integration.

In a series of recent experiments, we found that if rats are presented with two temporal cues, each signifying that reward will be delivered after a different duration elapses (e.g., tone-10 seconds / light-20 seconds), they will behave as if they have computed a weighted average of these respective durations.

Temporal averaging across multiple response options: insight into the mechanisms underlying integration.

Rats trained on a dual-duration, dual-modality peak-interval procedure (e.g., tone = 10 s/light = 20 s) often show unimodal response distributions with peaks that fall in between the anchor durations when both cues are presented as a simultaneous compound.

Prevalence of low bone mineral density in adolescents and adults with cystic fibrosis.

Objective: The aim of this cross-sectional study was to evaluate the prevalence of low bone mass density in cystic fibrosis patients as well as to evaluate the factors associated with bone mass in such patients.

Methods: Bone mass density was measured by dual-photon X-ray absorptiometry of lumbar spine (L1-L4), in patients ≤19 years old, or lumbar spine and femur (total and neck) in patients ≥20 years old. Evaluations of nutritional status, biochemical parameters, and lung function were performed.

Hypovitaminosis D in patients with cystic fibrosis: a cross-section study in South Brazil.

Introduction: Cystic fibrosis (CF) patients have a susceptibility to vitamin D deficiency because of nutrient malabsorption.

Objectives: To evaluate the prevalence of hypovitaminosis D in CF patients and the factors associated with serum 25-hydroxyvitamin D levels.

Methods: We evaluated the prevalence of vitamin D deficiency defined as 25-hydroxyvitamin D <30 ng/mL, as suggested recently by the Cystic Fibrosis Foundation, and factors associated with its serum levels.

The delivery of heavy menstrual bleeding services in England and Wales after publication of national guidelines: a survey of hospitals.

Background: In 2007-2008, two UK-based organisations, the National Institute for Health and Clinical Excellence and the Royal College of Obstetricians and Gynaecologists, published guidelines for the management of care and organisation of outpatient services for women with heavy menstrual bleeding (HMB). In 2010, this study was conducted to provide an update on guideline-related services provided in England and Wales, and whether they are consistent with national clinical guidelines two to three years after publication.

Methods: An organisational survey of outpatient gynaecology clinics was conducted of 221 hospitals in 154 acute National Health Service (NHS) trusts in England and Wales.

[Music therapy on Parkinson disease].

This study is a result of a qualitative research, in the Gerontology and Music therapy scenario. It was analyzed the importance of alternative practices like playing an instrument (piano, violin, etc.), singing, or practicing a guided musical exercise as a therapy activity for elder people with Parkinson Disease.

TMC125, a novel next-generation nonnucleoside reverse transcriptase inhibitor active against nonnucleoside reverse transcriptase inhibitor-resistant human immunodeficiency virus type 1.

Nonnucleoside reverse transcriptase inhibitors (NNRTIs) are potent inhibitors of human immunodeficiency virus type 1 (HIV-1); however, currently marketed NNRTIs rapidly select resistant virus, and cross-resistance within the class is extensive. A parallel screening strategy was applied to test candidates from a series of diarylpyrimidines against wild-type and resistant HIV strains carrying clinically relevant mutations. Serum protein binding and metabolic stability were addressed early in the selection process.

Piperidine-containing beta-arylpropionic acids as potent antagonists of alphavbeta3/alphavbeta5 integrins.

The synthesis and SAR of a new class of piperidine-based alphavbeta3/alphavbeta5 integrin antagonists is described. Replacement of an amide bond in a prototype isonipecotamide by a C-C isostere, and adjustment of the spacer length between the carboxylic acid and basic moieties, led to low nanomolar antagonists of alphavbeta3 and/or alphavbeta5 integrins with excellent selectivity versus alpha(IIb)beta3.

Roles of conformational and positional adaptability in structure-based design of TMC125-R165335 (etravirine) and related non-nucleoside reverse transcriptase inhibitors that are highly potent and effective against wild-type and drug-resistant HIV-1 variants.

Anti-AIDS drug candidate and non-nucleoside reverse transcriptase inhibitor (NNRTI) TMC125-R165335 (etravirine) caused an initial drop in viral load similar to that observed with a five-drug combination in naïve patients and retains potency in patients infected with NNRTI-resistant HIV-1 variants. TMC125-R165335 and related anti-AIDS drug candidates can bind the enzyme RT in multiple conformations and thereby escape the effects of drug-resistance mutations. Structural studies showed that this inhibitor and other diarylpyrimidine (DAPY) analogues can adapt to changes in the NNRTI-binding pocket in several ways: (1).