A unique multi-synaptic mechanism involving acetylcholine and GABA regulates dopamine release in the nucleus accumbens through early adolescence in male rats.

Adolescence is characterized by changes in reward-related behaviors, social behaviors, and decision-making. These behavioral changes are necessary for the transition into adulthood, but they also increase vulnerability to the development of a range of psychiatric disorders. Major reorganization of the dopamine system during adolescence is thought to underlie, in part, the associated behavioral changes and increased vulnerability.

How Does Chronobiology Contribute to the Development of Diseases in Later Life.

An increasingly older population is one of the major social and medical challenges we currently face. Between 2010 and 2050, it is estimated that the proportion of adults over 65 years of age will double from 8% to 16% of the global population. A major concern associated with aging is the changes in health that can lead to various diseases such as cancer and neurogenerative diseases, which are major burdens on individuals and societies.

Cell-Selective Adeno-Associated Virus-Mediated Gene Regulation Therapy Rescues Mortality and Seizure Phenotypes in a Dravet Syndrome Mouse Model and Is Well Tolerated in Nonhuman Primates.

Dravet syndrome (DS) is a developmental and epileptic encephalopathy caused by monoallelic loss-of-function variants in the gene. encodes for the alpha subunit of the voltage-gated type I sodium channel (Na1.1), the primary voltage-gated sodium channel responsible for generation of action potentials in GABAergic inhibitory interneurons.

Diurnal rhythms in cholinergic modulation of rapid dopamine signals and associative learning in the striatum.

Dysregulation of biological rhythms plays a role in a wide range of psychiatric disorders. We report mechanistic insights into the rhythms of rapid dopamine signals and cholinergic interneurons (CINs) working in concert in the rodent striatum. These rhythms mediate diurnal variation in conditioned responses to reward-associated cues.

Comparing dopamine release, uptake, and D2 autoreceptor function across the ventromedial to dorsolateral striatum in adolescent and adult male and female rats.

Adolescence is characterized by changes in behavior, such as increases in sensation seeking and risk taking, and increased vulnerability to developing a range of psychiatric disorders, including substance abuse disorders (SUD) and mood disorders. The mesolimbic dopamine system plays an essential role in mediating these behaviors and disorders. Therefore, it is imperative to understand how the dopamine system and its regulation are changing during this period of development.

Human Bacterial Artificial Chromosome (BAC) Transgenesis Fully Rescues Noradrenergic Function in Dopamine β-Hydroxylase Knockout Mice.

Dopamine β-hydroxylase (DBH) converts dopamine (DA) to norepinephrine (NE) in noradrenergic/adrenergic cells. DBH deficiency prevents NE production and causes sympathetic failure, hypotension and ptosis in humans and mice; DBH knockout (Dbh -/-) mice reveal other NE deficiency phenotypes including embryonic lethality, delayed growth, and behavioral defects. Furthermore, a single nucleotide polymorphism (SNP) in the human DBH gene promoter (-970C>T; rs1611115) is associated with variation in serum DBH activity and with several neurological- and neuropsychiatric-related disorders, although its impact on DBH expression is controversial.

A Method for Psychosocial Stress-Induced Reinstatement of Cocaine Seeking in Rats.

We describe a novel preclinical model of stress-induced relapse to cocaine use in rats using social defeat stress, an ethologically valid psychosocial stressor in rodents that closely resembles stressors that promote craving and relapse in humans. Rats self-administered cocaine for 20 days. On days 11, 14, 17, and 20, animals were subjected to social defeat stress or a nonstressful control condition following the session, with discrete environmental stimuli signaling the impending event.

Transcriptional program of ciliated epithelial cells reveals new cilium and centrosome components and links to human disease.

Defects in the centrosome and cilium are associated with a set of human diseases having diverse phenotypes. To further characterize the components that define the function of these organelles we determined the transcriptional profile of multiciliated tracheal epithelial cells. Cultures of mouse tracheal epithelial cells undergoing differentiation in vitro were derived from mice expressing GFP from the ciliated-cell specific FOXJ1 promoter (FOXJ1:GFP).

Methylation by Set9 modulates FoxO3 stability and transcriptional activity.

The FoxO family of transcription factors plays an important role in longevity and tumor suppression by regulating the expression of a wide range of target genes. FoxO3 has recently been found to be associated with extreme longevity in humans and to regulate the homeostasis of adult stem cell pools in mammals, which may contribute to longevity. The activity of FoxO3 is controlled by a variety of post-translational modifications that have been proposed to form a 'code' affecting FoxO3 subcellular localization, DNA binding ability, protein-protein interactions and protein stability.

The centriolar satellite proteins Cep72 and Cep290 interact and are required for recruitment of BBS proteins to the cilium.

Defects in centrosome and cilium function are associated with phenotypically related syndromes called ciliopathies. Centriolar satellites are centrosome-associated structures, defined by the protein PCM1, that are implicated in centrosomal protein trafficking. We identify Cep72 as a PCM1-interacting protein required for recruitment of the ciliopathy-associated protein Cep290 to centriolar satellites.

A shared molecular mechanism underlies the human rasopathies Legius syndrome and Neurofibromatosis-1.

The Ras/mitogen-activated protein kinase (MAPK) pathway plays a critical role in transducing mitogenic signals from receptor tyrosine kinases. Loss-of-function mutations in one feedback regulator of Ras/MAPK signaling, SPRED1 (Sprouty-related protein with an EVH1 domain), cause Legius syndrome, an autosomal dominant human disorder that resembles Neurofibromatosis-1 (NF1). Spred1 functions as a negative regulator of the Ras/MAPK pathway; however, the underlying molecular mechanism is poorly understood.

Kinetics and longevity of ΦC31 integrase in mouse liver and cultured cells.

The ΦC31 integrase system provides genomic integration of plasmid DNA that may be useful in gene therapy. For example, the ΦC31 system has been used in combination with hydrodynamic injection to achieve long-term expression of factor IX in mouse liver. However, a concern is that prolonged expression of ΦC31 integrase within cells could potentially stimulate chromosome rearrangements or an immune response.

The effects of chlorhexidine gluconate (0.12%) on the antimicrobial properties of tooth-colored ProRoot mineral trioxide aggregate.

The purpose of this in vitro study was to determine whether the substitution of 0.12% chlorhexidine gluconate for sterile water as a mixing agent would enhance the antimicrobial activity of tooth-colored ProRoot mineral trioxide aggregate (MTA) against Actinomyces odontolyticus (ATCC17982), Fusobacterium nucleatum (ATCC2586), Streptococcus sanguis (ATCC10556), Enterococcus faecalis (ER3/2S), Escherichia coli (SM10lambdapir), Staphylococcus aureus (ATCC6538), Pseudomonas aeruginosa (UME), and Candida albicans (ATCC10261). Two wells of 5-mm diameter were made in triplicate agar plates inoculated with standardized suspensions of each microorganism.

Electron spin relaxation near a micron-size ferromagnet.

Magnetic resonance force microscopy was used to study the behavior of small ensembles of unpaired electron spins in silica near a micrometer-size ferromagnetic tip. Using a cantilever-driven spin manipulation protocol and a magnetic field gradient greater than 10(5) T/m, signals from as few as 100 net spins within a 20 nm thick resonant slice could be studied. A sixfold increase in the spin-lattice relaxation rate was found within 800 nm of the ferromagnet, while no effect due to silica surface proximity was detected.

Noncontact friction and force fluctuations between closely spaced bodies.

Noncontact friction between a Au(111) surface and an ultrasensitive gold-coated cantilever was measured as a function of tip-sample spacing, temperature, and bias voltage using observations of cantilever damping and Brownian motion. The importance of the inhomogeneous contact potential is discussed and comparison is made to measurements over dielectric surfaces. Using the fluctuation-dissipation theorem, the force fluctuations are interpreted in terms of near-surface fluctuating electric fields interacting with static surface charge.

Magnetic dissipation and fluctuations in individual nanomagnets measured by ultrasensitive cantilever magnetometry.

Cantilever magnetometry with moment resolution better than 10(4)micro(B) was used to study individual nanomagnets. By using the fluctuation-dissipation theorem to interpret measurements of field-induced cantilever damping, the low frequency spectral density of magnetic fluctuations could be determined with resolution better than 1micro(B) Hz-1/2. Cobalt nanowires exhibited significant magnetic dissipation and the associated magnetic fluctuations were found to have 1/f frequency dependence.

Delta hepatitis virus infection in China.

To assess the prevalence, epidemiological features and prognostic implications of hepatitis D (Delta) in Sichuan Province, The People's Republic of China, 649 sera (515 from HBsAg positive patients and 134 from HBsAg negative subjects) were tested by radioimmunoassay (RIA) for antibody to the hepatitis D virus (anti-HD). Forty-seven sera (7.2%) showed some degree of reactivity.

The prevalence of antibody to delta virus in western Canada.

To assess the prevalence and pathological role of hepatitis D virus (HDV) infection in western Canada, we tested a total of 310 sera from the province of Alberta, Yukon and Northwest Territories for antibody to HD (anti-HDV) by commercial solid phase radioimmunoassay. Two hundred and forty-five sera were hepatitis B surface antigen (HBsAg) positive. These were classified on the basis of clinical and biochemical data as either acute hepatitis, chronic hepatitis or in the healthy carrier phase of infection Sixty-five HBsAg negative sera from patients with other forms of chronic liver diseases served as controls.