Conservation of a Chromosome 8 Inversion and Exon Mutations Confirm Common Gulonolactone Oxidase Gene Evolution Among Primates, Including H. Neanderthalensis.

Ascorbic acid functions as an antioxidant and facilitates other biochemical processes such as collagen triple helix formation, and iron uptake by cells. Animals which endogenously produce ascorbic acid have a functional gulonolactone oxidase gene (GULO); however, humans have a GULO pseudogene (GULOP) and depend on dietary ascorbic acid. In this study, the conservation of GULOP sequences in the primate haplorhini suborder were investigated and compared to the GULO sequences belonging to the primates strepsirrhini suborder.

Non-Coding RNAs in Human Health and Diseases.

Non-coding RNAs (ncRNAs) are, arguably, the enigma of the RNA transcriptome. Even though there are more annotated ncRNAs (25,967) compared to mRNAs (19,827), we know far less about each of the genes that produce ncRNA, especially in terms of their regulation, molecular functions, and interactions. Further, we are only beginning to understand the role of differential regulation or function of ncRNAs caused by genetic and epigenetic perturbations, such as single nucleotide variants (SNV), deletions, insertions, and histone/DNA modifications.

In Silico Examination of Single Nucleotide Missense Mutations in , a Gene Linked to Infertility and Obesity.

Continual advances in our understanding of the human genome have led to exponential increases in known single nucleotide variants. The characterization of each of the variants lags behind. For researchers needing to study a single gene, or multiple genes in a pathway, there must be ways to narrow down pathogenic variants from those that are silent or pose less pathogenicity.

Analysis of : A Long Non-Coding RNA Hosting , Whose Loss Contributes to Prader-Willi Syndrome Etiology.

The Small Nucleolar Host Gene 14 () is a host gene for small non-coding RNAs, including the small nucleolar C/D box RNA encoding locus. Large deletions of the locus, as well as microdeletions of the locus, lead to the neurodevelopmental genetic disorder Prader-Willi syndrome. This review will focus on the gene, its expression patterns, its role in human cancer, and the possibility that single nucleotide variants within the locus contribute to human phenotypes in the general population.

The living donor evaluation as a life-saving event.

Background: As a population, living kidney donors have a longer life expectancy than the general population. This is generally thought to be an artifact of selection, as only healthy individuals are allowed to donate, and the operative mortality and risk of subsequent renal failure are very low. However, there may also be an additional benefit to the process, as the donor evaluation may uncover an early occult cancer or a potentially serious medical problem.

Dietary Conjugated Linoleic Acid Reduces Body Weight and Fat in and Mouse Models of Prader-Willi Syndrome.

Prader-Willi Syndrome (PWS) is a human genetic condition that affects up to 1 in 10,000 live births. Affected infants present with hypotonia and developmental delay. Hyperphagia and increasing body weight follow unless drastic calorie restriction is initiated.

Inactivating NHLH2 variants cause idiopathic hypogonadotropic hypogonadism and obesity in humans.

Metabolism has a role in determining the time of pubertal development and fertility. Nonetheless, molecular/cellular pathways linking metabolism/body weight to puberty/reproduction are unknown. The KNDy (Kisspeptin/Neurokinin B/Dynorphin) neurons in the arcuate nucleus of the hypothalamus constitute the GnRH (gonadotropin-releasing hormone) pulse generator.

Searching for Gravitational Waves from Cosmological Phase Transitions with the NANOGrav 12.5-Year Dataset.

We search for a first-order phase transition gravitational wave signal in 45 pulsars from the NANOGrav 12.5-year dataset. We find that the data can be modeled in terms of a strong first order phase transition taking place at temperatures below the electroweak scale.

Microaggressions and Coping with Linkages for Mentoring.

Microaggressions can have damaging health impacts on minority groups experiencing exclusion through such forms of discrimination and bias. Using focus groups of different marginalized groups and through in-depth interviewing, we analyze the ways in which marginalized identities respond to and deal with microaggressions and highlight some relevant linkages to mentoring. Through a qualitative analysis of microaggression experiences, along the lines of race, gender, sexual orientation, and religion, we explore different coping mechanisms and potential linkages to mentoring.

Snord116 Post-transcriptionally Increases Nhlh2 mRNA Stability: Implications for Human Prader-Willi Syndrome.

The smallest genomic region causing Prader-Willi Syndrome (PWS) deletes the non-coding RNA SNORD116 cluster; however, the function of SNORD116 remains a mystery. Previous work in the field revealed the tantalizing possibility that expression of NHLH2, a gene previously implicated in both obesity and hypogonadism, was downregulated in PWS patients and differentiated stem cells. In silico RNA: RNA modeling identified several potential interaction domains between SNORD116 and NHLH2 mRNA.

New gene targets in the study of hypogonadotropic hypogonadism.

The incidence of congenital hypogonadotropic hypogonadism (HH) is approximately 1-10 in 100,000 live births. Known syndromes, such as Kallman syndrome, caused by a mutation in the KAL-1 gene, and other genes listed in the Online Mendelian Inheritance in Man database, account for 2/3 of the cases. The rest of these cases where there is no known genetic cause for HH are termed idiopathic.

A low-cost, in silico nutritional genomics course-based undergraduate research experience applicable to multiple disciplines.

This article describes the development and assessment of a Nutritional Genomics course, designed to be held in a regular classroom during normal class periods, with few extra costs to the students or the department. The course was run as an upper-level undergraduate and lower-level graduate student course. Student taking the course spent 11 weeks learning and then 4 weeks using various in silico methods to independently characterize genes of interest in the field.

Pro-opiomelanocortin Neurons and the Transcriptional Regulation of Motivated Exercise.

Hypothalamic pro-opiomelanocortin (POMC) neurons are key sensory neurons for energy balance. The basic helix-loop-helix transcription factor NHLH2 is expressed in POMC neurons, and Nhlh2 knockout mice show adult-onset obesity with low exercise behavior. Evidence is presented to explore the hypothesis that NHLH2 transcriptional activity within POMC neurons is crucial for maintaining motivated spontaneous activity and enforced exercise.

Phylogenetic Analysis of the SNORD116 Locus.

The small nucleolar RNA locus () is contained within the long noncoding RNA host gene on human chromosome 15q11-q13. The locus is a cluster of 28 or more small nucleolar (sno) RNAs; C/D box (SNORDs). Individual RNAs within the cluster are tandem, highly similar sequences, referred to as , , etc.

Protocol of the KTFT-TALK study to reduce racial disparities in kidney transplant evaluation and living donor kidney transplantation.

Living donor kidney transplantation (LDKT) is the optimal treatment for end-stage kidney disease (ESKD). The evaluation process for a kidney transplant is complex, time consuming, and burdensome to the ESKD patient. Also, race disparities exist in rates of transplant evaluation completion, transplantation, and LDKT.

A molecular conundrum involving hypothalamic responses to and roles of long non-coding RNAs following food deprivation.

Long non-coding RNAs (lncRNAs) are one of most poorly understood RNA classes in the mammalian transcriptome. However, they are emerging as important players in transcriptional regulation, especially within the complexity of the nervous system. This review summarizes the known information about lncRNAs, and their roles in endocrine processes, as well as the lesser-known information about lncRNAs in the brain, and in the neuroendocrine hypothalamus.

Characterization of the hypothalamic transcriptome in response to food deprivation reveals global changes in long noncoding RNA, and cell cycle response genes.

The hypothalamus integrates energy balance information from the periphery using different neuronal subtypes within each of the hypothalamic areas. However, the effects of prandial state on global mRNA, microRNA and long noncoding (lnc) RNA expression within the whole hypothalamus are largely unknown. In this study, mice were given either a 24-h fast, or ad libitum access to food.

A Genetic Basis for Motivated Exercise.

Prior research has demonstrated a genetic basis for motivated exercise, with evidence of a role for nescient helix-loop-helix-2 (NHLH2/Nhlh2). Nhlh2 transcriptionally regulates the monoamine oxidase A (MAO-A) gene. This article examines the evidence for the hypothesis that polymorphisms in NHLH2 or MAO-A contribute to differences in the human motivation for exercise and physical activity.

Effects of postweaning administration of conjugated linoleic acid on development of obesity in nescient basic helix-loop-helix 2 knockout mice.

Conjugated linoleic acid (CLA) has been reported to prevent body weight gain and fat accumulation in part by improving physical activity in mice. However, the effects of postweaning administration of CLA on the development of obesity later in life have not yet been demonstrated. The current study investigated the role of postweaning CLA treatment on skeletal muscle energy metabolism in genetically induced inactive adult-onset obese model, nescient basic helix-loop-helix 2 knockout (N2KO) mice.

Mitigating or exacerbating effects of maternal-fetal programming of female mice through the food choice environment.

Humans live, eat, and become overweight/obese in complex surroundings where there are many available food choices. Prenatal exposure to poor food choices predisposes offspring to increased negative health risks, including obesity. Many animal experiments have analyzed intergenerational body weight parameters in an environment without food choices, which may not be directly translatable to the human food environment.

Leptin signaling regulates hypothalamic expression of nescient helix-loop-helix 2 (Nhlh2) through signal transducer and activator 3 (Stat3).

Mice with a deletion of the hypothalamic basic helix-loop-helix transcription factor Nhlh2 display adult onset obesity. We have previously shown that Nhlh2 expression is induced by leptin. In this study, we identify a small proximal leptin-responsive promoter region in the Nhlh2 gene.