Responsive Versus Continuous Deep Brain Stimulation for Speech in Essential Tremor: A Pilot Study.

Background: Responsive deep brain stimulation (rDBS) uses physiological signals to deliver stimulation when needed. rDBS is hypothesized to reduce stimulation-induced speech effects associated with continuous DBS (cDBS) in patients with essential tremor (ET).

Objective: To determine if rDBS reduces cDBS speech-related side effects while maintaining tremor suppression.

Intestinal Carnitine Status and Fatty Acid Oxidation in Response to Clofibrate and Medium-Chain Triglyceride Supplementation in Newborn Pigs.

To investigate the role of peroxisome proliferator-activated receptor alpha (PPARα) in carnitine status and intestinal fatty acid oxidation in neonates, a total of 72 suckled newborn piglets were assigned into 8 dietary treatments following a 2 (±0.35% clofibrate) × 4 (diets with: succinate+glycerol (Succ), tri-valerate (TC5), tri-hexanoate (TC6), or tri-2-methylpentanoate (TMPA)) factorial design. All pigs received experimental milk diets with isocaloric energy for 5 days.

Global gene expression analysis of the turkey hen hypothalamo-pituitary-gonadal axis during the preovulatory hormonal surge.

The preovulatory hormonal surge (PS) consists of elevated circulating luteinizing hormone (LH) and progesterone levels and serves as the primary trigger for ovarian follicle ovulation. Increased LH and progesterone, produced by the pituitary and the granulosa layer of the largest ovarian follicle (F1), respectively, result from hypothalamic stimulation and steroid hormone feedback on the hypothalamo-pituitary-gonadal (HPG) axis. The hypothalamus, pituitary, F1 granulosa, and granulosa layer of the fifth largest follicle (F5) were isolated from converter turkey hens outside and during the PS and subjected to RNA sequencing (n = 6 per tissue).

Alterations in hepatic mitotic and cell cycle transcriptional networks during the metabolic switch in broiler chicks.

During embryonic life, chicks mainly derive energy from hepatic oxidation of yolk lipids. After hatch, chicks must rely on carbohydrate-rich feed to obtain energy. This requires an abrupt and intensive switch of metabolic processes, particularly in the liver.

Transcriptome Analysis During Follicle Development in Turkey Hens With Low and High Egg Production.

Low and high egg producing hens exhibit gene expression differences related to ovarian steroidogenesis. High egg producing hens display increased expression of genes involved in progesterone and estradiol production, in the granulosa layer of the largest follicle (F1G) and small white follicles (SWF), respectively, whereas low egg producing hens display increased expression of genes related to progesterone and androgen production in the granulosa (F5G) and theca interna layer (F5I) of the fifth largest follicle, respectively. Transcriptome analysis was performed on F1G, F5G, F5I, and SWF samples from low and high egg producing hens to identify novel regulators of ovarian steroidogenesis.

Centennial Review: Metabolic microRNA - shifting gears in the regulation of metabolic pathways in poultry.

Over 20 yr ago, a small noncoding class of RNA termed microRNA (miRNA) that was able to recognize sequences in mRNAs and inhibit their translation was discovered in Caenorhabditis elegans. In the intervening years, miRNA have been discovered in most eukaryotes and are now known to regulate the majority of protein-coding genes. It has been discovered that disruption of miRNA function often leads to the development of pathological conditions.

Expression Signatures of microRNAs and Their Targeted Pathways in the Adipose Tissue of Chickens during the Transition from Embryonic to Post-Hatch Development.

As the chick transitions from embryonic to post-hatching life, its metabolism must quickly undergo a dramatic switch in its major energy source. The chick embryo derives most of its energy from the yolk, a lipid-rich/carbohydrate-poor source. Upon hatching, the chick's metabolism must then be able to utilize a lipid-poor/carbohydrate-rich source (feed) as its main form of energy.

Transcriptional Immune Signatures of Alveolar Macrophages and the Impact of the NLRP3 Inflammasome on Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) Replication.

Porcine Reproductive and Respiratory Syndrome (PRRS) is a contagious viral (PRRSV) disease in pigs characterized by poor reproductive health, increased mortality, and reductions in growth rates. PRRSV is known to implement immuno-antagonistic mechanisms to evade detection and mute host responses to infection. To better understand the cellular immunosignature of PRRSV we have undertaken transcriptome and immunomodulatory studies in PRRSV-infected porcine alveolar macrophages (PAMs).

Transcriptome analysis of the hypothalamus and pituitary of turkey hens with low and high egg production.

Background: High egg producing hens (HEPH) show increased hypothalamic and pituitary gene expression related to hypothalamo-pituitary-gonadal (HPG) axis stimulation as well as increased in vitro responsiveness to gonadotropin releasing hormone (GnRH) stimulation in the pituitary when compared to low egg producing hens (LEPH). Transcriptome analysis was performed on hypothalamus and pituitary samples from LEPH and HEPH to identify novel regulators of HPG axis function.

Results: In the hypothalamus and pituitary, 4644 differentially expressed genes (DEGs) were identified between LEPH and HEPH, with 2021 genes up-regulated in LEPH and 2623 genes up-regulated in HEPH.

Delayed Feeding Alters Transcriptional and Post-Transcriptional Regulation of Hepatic Metabolic Pathways in Peri-Hatch Broiler Chicks.

Hepatic fatty acid oxidation of yolk lipoproteins provides the main energy source for chick embryos. Post-hatching these yolk lipids are rapidly exhausted and metabolism switches to a carbohydrate-based energy source. We recently demonstrated that many microRNAs (miRNAs) are key regulators of hepatic metabolic pathways during this metabolic switching.

Impact of HVT Vaccination on Splenic miRNA Expression in Marek's Disease Virus Infections.

Marek's Disease is a lymphoproliferative disease of chickens caused by Marek's Disease Virus. Similar to other herpesviruses, Marek's Disease Virus (MDV) encodes its own small non-coding regulatory RNAs termed microRNAs (miRNAs). We previously found that the expression profile of these viral miRNAs is affected by vaccination with Herpesvirus of Turkeys (HVT).

Alterations in cellular and viral microRNA and cellular gene expression in Marek's disease virus-transformed T-cell lines treated with sodium butyrate.

A shared feature of herpesviruses is their ability to enter a latent state following an initially lytic infection. Marek's disease virus serotype 1 (MDV-1) is an oncogenic avian herpesvirus. Small RNA profiling studies have suggested that microRNAs (miRNAs) are involved in viral latency.

Interaction of porcine reproductive and respiratory syndrome virus major envelope proteins GP5 and M with the cellular protein Snapin.

Background: Porcine reproductive and respiratory syndrome (PRRS) is characterized by abortions in pregnant sows and respiratory disease, particularly in young pigs. The causative agent is porcine reproductive and respiratory syndrome virus (PRRSV), a member of the arterivirus family. GP5 and M are the major envelope proteins encoded by PRRSV.

Identification of microRNAs controlling hepatic mRNA levels for metabolic genes during the metabolic transition from embryonic to posthatch development in the chicken.

Background: The transition from embryonic to posthatch development in the chicken represents a massive metabolic switch from primarily lipolytic to primarily lipogenic metabolism. This metabolic switch is essential for the chick to successfully transition from the metabolism of stored egg yolk to the utilization of carbohydrate-based feed. However, regulation of this metabolic switch is not well understood.

Interdisciplinary Parkinson's Disease Deep Brain Stimulation Screening and the Relationship to Unintended Hospitalizations and Quality of Life.

Objective: To investigate the impact of pre-operative deep brain stimulation (DBS) interdisciplinary assessments on post-operative hospitalizations and quality of life (QoL).

Background: DBS has been utilized successfully in Parkinson's disease (PD) for the treatment of tremor, rigidity, bradykinesia, off time, and motor fluctuations. Although DBS is becoming a more common management approach there are no standardized criteria for selection of DBS candidates, and sparse data exist to guide the use of interdisciplinary evaluations for DBS screening.

Discovery of a Novel Class of Imidazo[1,2-a]Pyridines with Potent PDGFR Activity and Oral Bioavailability.

The in silico construction of a PDGFRβ kinase homology model and ensuing medicinal chemistry guided by molecular modeling, led to the identification of potent, small molecule inhibitors of PDGFR. Subsequent exploration of structure-activity relationships (SAR) led to the incorporation of a constrained secondary amine to enhance selectivity. Further refinements led to the integration of a fluorine substituted piperidine, which resulted in significant reduction of P-glycoprotein (Pgp) mediated efflux and improved bioavailability.

Involvement of eukaryotic small RNA pathways in host defense and viral pathogenesis.

Post-transcriptional gene regulation by small RNAs is now established as an important branch of the gene regulatory system. Many different classes of small RNAs have been discovered; among these are short interfering RNAs (siRNAs) and microRNA (miRNAs). Though differences in the processing and function of small RNAs exist between plants and animals, both groups utilize small RNA-mediated gene regulation in response to pathogens.

The interplay between MDV and HVT affects viral miRNa expression.

It is well established that herpesviruses encode numerous microRNAs (miRNAs) and that these virally encoded small RNAs play multiple roles in infection. The present study was undertaken to determine how co-infection of a pathogenic MDV serotype one (MDV1) strain (MD5) and a vaccine strain (herpesvirus of turkeys [HVT]) alters viral miRNA expression in vivo. We first used small RNA deep sequencing to identify MDV1-encoded miRNAs that are expressed in tumorigenic spleens of MDV1-infected birds.

Current state of Marek's disease virus microRNA research.

MicroRNA (miRNA) is a major family of small RNAs that posttranscriptionally regulate gene expression. Small RNA profiling studies have revealed that some viruses, particularly large DNA viruses, such as Marek's disease virus (MDV), encode their own set of miRNAs. There are currently 406 viral miRNAs in miRBase, of which 392 are encoded by herpesviruses.

Characterization of miR-10a mediated gene regulation in avian splenocytes.

It is well established that microRNAs (miRNAs) are an important class of post-transcriptional regulators of gene expression. Although numerous miRNA expression profiles have been generated for many eukaryotic organisms, little is known about the specific functions of individual miRNAs in regulating gene expression. We previously reported that the miRNA, miR-10a, is highly expressed during spleen development in embryonic chicks.

Discovery of chicken microRNAs associated with lipogenesis and cell proliferation.

The primary function of microRNA (miRNA, a class of small regulatory RNA) is to regulate gene expression. Studies of miRNA in mammals suggest that many liver-associated miRNAs are expressed, with a wide range of functions. To characterize miRNA expressed in the avian liver, we created two small RNA libraries from embryonic chick livers at embryonic day (E)15 and E20, a time at which the embryo begins to grow rapidly and so its energy demands increase.

Identification of microRNA in the developing chick immune organs.

MicroRNAs (miRNAs) are small (approximately 19-24 nt) noncoding RNAs that participate in posttranscriptionally regulating gene expression. MicroRNAs display very dynamic expression patterns with many being expressed in a temporal as well as a spatial manner. Immune genes have been shown to have a higher propensity for miRNA target sites compared to the rest of the genome, thus suggesting that miRNA are key regulators of the immune system.

Divergence of protein kinase A catalytic subunits in Cryptococcus neoformans and Cryptococcus gattii illustrates evolutionary reconfiguration of a signaling cascade.

Gene duplication and divergence via both the loss and gain of gene activities are powerful evolutionary forces underlying the origin of new biological functions. Here a comparative genetics approach was applied to examine the roles of protein kinase A (PKA) catalytic subunits in three closely related varieties or sibling species of the pathogenic fungus genus Cryptococcus. Previous studies revealed that two PKA catalytic subunits, Pka1 and Pka2, control virulence factor production and mating.

Pde1 phosphodiesterase modulates cyclic AMP levels through a protein kinase A-mediated negative feedback loop in Cryptococcus neoformans.

The virulence of the human pathogenic fungus Cryptococcus neoformans is regulated by a cyclic AMP (cAMP)-dependent protein kinase A (PKA) signaling cascade that promotes mating and the production of melanin and capsule. In this study, genes encoding homologs of the Saccharomyces cerevisiae low- and high-affinity phosphodiesterases, PDE1 and PDE2, respectively, were deleted in serotype A strains of C. neoformans.

Adenylyl cyclase-associated protein Aca1 regulates virulence and differentiation of Cryptococcus neoformans via the cyclic AMP-protein kinase A cascade.

The evolutionarily conserved cyclic AMP (cAMP) signaling pathway controls cell functions in response to environmental cues in organisms as diverse as yeast and mammals. In the basidiomycetous human pathogenic fungus Cryptococcus neoformans, the cAMP pathway governs virulence and morphological differentiation. Here we identified and characterized adenylyl cyclase-associated protein, Aca1, which functions in parallel with the Galpha subunit Gpa1 to control the adenylyl cyclase (Cac1).