LNA blockers for improved amplification selectivity.

LNA-containing oligonucleotides bind DNA more tightly than standard DNA, so they can interact with targeted sequences and affect multiple processes. When a desired DNA is present at low concentrations relative to nearly identical undesired DNAs, LNAs can block amplification of unwanted DNAs. Using a short rAAV and synthetic DNA sequence as a model, we studied the length, number, and positioning of LNA bases to improve blocker effectiveness.

The Mediating Effect of Caregiving Relationship Quality on the Association Between Caregiving Stressors and Mental Health Problems Among Older Spousal Caregivers.

Providing care to a spouse can be especially challenging for older adults given their compounding stressors resulting from aging and caregiving. This cross-sectional study examines the relationships between caregiving stressors and caregiver mental health problems and the potential mediator (i.e.

"Intelligent Justice": human-centered considerations in China's legal AI transformation.

In recent years, the Chinese government and its judiciary have made a policy decision to leverage artificial intelligence in broader judicial reform efforts. The push to use AI to such a large extent in the judiciary is unique to China, influenced by chronic challenges facing the courts, including an exponential increase in casework and a shortage of qualified professionals in the judiciary. This has resulted in a number of pilot programs across the country that have produced various AI systems embedded in different areas of the judicial system.

Molecular characterization of precise in vivo targeted gene integration in human cells using AAVHSC15.

Targeted gene integration via precise homologous recombination (HR)-based gene editing has the potential to correct genetic diseases. AAV (adeno-associated virus) can mediate nuclease-free gene integration at a disease-causing locus. Therapeutic application of AAV gene integration requires quantitative molecular characterization of the edited sequence that overcome technical obstacles such as excess episomal vector genomes and lengthy homology arms.

Opposing Cholinergic and Serotonergic Modulation of Layer 6 in Prefrontal Cortex.

Prefrontal cortex is a hub for attention processing and receives abundant innervation from cholinergic and serotonergic afferents. A growing body of evidence suggests that acetylcholine (ACh) and serotonin (5-HT) have opposing influences on tasks requiring attention, but the underlying neurophysiology of their opposition is unclear. One candidate target population is medial prefrontal layer 6 pyramidal neurons, which provide feedback modulation of the thalamus, as well as feed-forward excitation of cortical interneurons.

Serotonergic Suppression of Mouse Prefrontal Circuits Implicated in Task Attention.

Serotonin (5-HT) regulates attention by neurobiological mechanisms that are not well understood. Layer 6 (L6) pyramidal neurons of prefrontal cortex play an important role in attention and express 5-HT receptors, but the serotonergic modulation of this layer and its excitatory output is not known. Here, we performed whole-cell recordings and pharmacological manipulations in acute brain slices from wild-type and transgenic mice expressing either eGFP or eGFP-channelrhodopsin in prefrontal L6 pyramidal neurons.

Dendritic spine density of prefrontal layer 6 pyramidal neurons in relation to apical dendrite sculpting by nicotinic acetylcholine receptors.

Prefrontal layer 6 (L6) pyramidal neurons play an important role in the adult control of attention, facilitated by their strong activation by nicotinic acetylcholine receptors. These neurons in mouse association cortex are distinctive morphologically when compared to L6 neurons in primary cortical regions. Roughly equal proportions of the prefrontal L6 neurons have apical dendrites that are "long" (reaching to the pial surface) vs.

Discrimination of closely related species in tintinnid ciliates: new insights on crypticity and polymorphism in the genus Helicostomella.

This study focuses on the utility of molecular markers for the discrimination of closely related species in tintinnid ciliates. We analyzed the ecologically important genus Helicostomella by sequencing part of the large-subunit rDNA (LSU rDNA) and the 5.8S rDNA combined with the internally transcribed spacer regions 1 and 2 (5.

Cholinergic excitation in mouse primary vs. associative cortex: region-specific magnitude and receptor balance.

Cholinergic stimulation of the cerebral cortex is essential for tasks requiring attention; however, there is still some debate over which cortical regions are required for such tasks. There is extensive cholinergic innervation of both primary and associative cortices, and transient release of acetylcholine (ACh) is detected in deep layers of the relevant primary and/or associative cortex, depending on the nature of the attention task. Here, we investigated the electrophysiological effects of ACh in layer VI, the deepest layer, of the primary somatosensory cortex, the primary motor cortex, and the associative medial prefrontal cortex.

Nicotinic acetylcholine receptors in attention circuitry: the role of layer VI neurons of prefrontal cortex.

Cholinergic modulation of prefrontal cortex is essential for attention. In essence, it focuses the mind on relevant, transient stimuli in support of goal-directed behavior. The excitation of prefrontal layer VI neurons through nicotinic acetylcholine receptors optimizes local and top-down control of attention.

Chrna5 genotype determines the long-lasting effects of developmental in vivo nicotine exposure on prefrontal attention circuitry.

Maternal smoking during pregnancy repeatedly exposes the developing fetus to nicotine and is linked with attention deficits in offspring. Corticothalamic neurons within layer VI of the medial prefrontal cortex are potential targets in the disruption of attention circuitry by nicotine, a process termed teratogenesis. These prefrontal layer VI neurons would be likely targets because they are developmentally excited and morphologically sculpted by a population of nicotinic acetylcholine receptors (nAChRs) that are sensitive to activation and/or desensitization by nicotine.

Plasticity of prefrontal attention circuitry: upregulated muscarinic excitability in response to decreased nicotinic signaling following deletion of α5 or β2 subunits.

Attention depends on cholinergic stimulation of nicotinic and muscarinic acetylcholine receptors in the medial prefrontal cortex. Pyramidal neurons in layer VI of this region express cholinergic receptors of both families and play an important role in attention through their feedback projections to the thalamus. Here, we investigate how nicotinic and muscarinic cholinergic receptors affect the excitability of these neurons using whole-cell recordings in acute brain slices of prefrontal cortex.