Publications by authors named "Kimberly H Cox"

Article Synopsis
  • Congenital hypogonadotropic hypogonadism (HH) is a genetic disorder that affects puberty and fertility, with 10-15% of cases showing potential for reversal.
  • A study of 240 men categorized three groups based on puberty status: fertile eunuchs (FE), absent puberty, and partial puberty; the FE group showed no history of micropenis and had distinctive hormonal profiles.
  • The FE group demonstrated higher levels of gonadotropins and a significant rate of spontaneous reversal, suggesting they experience milder neuroendocrine defects compared to other HH types, highlighting the FE variant as a potential predictor for reversibility in HH.
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Ultradian rhythms in metabolism and physiology have been described previously in mammals. However, the underlying mechanisms for these rhythms are still elusive. Here, we report the discovery of temperature-sensitive ultradian rhythms in mammalian fibroblasts that are independent of both the cell cycle and the circadian clock.

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Circadian (24-h) rhythms dictate almost everything we do, setting our clocks for specific times of sleeping and eating, as well as optimal times for many other basic functions. The physiological systems that coordinate circadian rhythms are intricate, but at their core, they all can be distilled down to cell-autonomous rhythms that are then synchronized within and among tissues. At first glance, these cell-autonomous rhythms may seem rather straight-forward, but years of research in the field has shown that they are strikingly complex, responding to many different external signals, often with remarkable tissue-specificity.

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The suprachiasmatic nucleus (SCN) is the master circadian pacemaker in mammals and is entrained by environmental light. However, the molecular basis of the response of the SCN to light is not fully understood. We used RNA/chromatin immunoprecipitation/single-nucleus sequencing with circadian behavioral assays to identify mouse SCN cell types and explore their responses to light.

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Patients with sleeping sickness, caused by the parasite , have disruptions in both sleep timing and sleep architecture. However, the underlying cause of these sleep disturbances is not well understood. Here, we assessed the sleep architecture of male mice infected with and found that infected mice had drastically altered sleep patterns.

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The suprachiasmatic nucleus (SCN) acts as a master pacemaker driving circadian behavior and physiology. Although the SCN is small, it is composed of many cell types, making it difficult to study the roles of particular cells. Here we develop bioluminescent circadian reporter mice that are Cre dependent, allowing the circadian properties of genetically defined populations of cells to be studied in real time.

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Circadian oscillations are generated via transcriptional-translational negative feedback loops. However, individual cells from fibroblast cell lines have heterogeneous rhythms, oscillating independently and with different period lengths. Here we showed that heterogeneity in circadian period is heritable and used a multi-omics approach to investigate underlying mechanisms.

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Nongenetic cellular heterogeneity is associated with aging and disease. However, the origins of cell-to-cell variability are complex and the individual contributions of different factors to total phenotypic variance are still unclear. Here, we took advantage of clear phenotypic heterogeneity of circadian oscillations in clonal cell populations to investigate the underlying mechanisms of cell-to-cell variability.

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Fumarylacetoacetate hydrolase (FAH) is the last enzyme in tyrosine catabolism, and mutations in the gene are associated with hereditary tyrosinemia type I (HT1 or TYRSN1) in humans. In a behavioral screen of -ethyl--nitrosourea mutagenized mice we identified a mutant line which we named "" (, MGI:3611216) with a nonsynonymous point mutation (N68S) in that caused age-dependent disruption of sleep-wake patterns. Mice homozygous for the mutation had an earlier onset of activity (several hours before lights off) and a reduction in total activity and body weight when compared with wild-type or heterozygous mice.

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The mammalian circadian clock has evolved as an adaptation to the 24-h light/darkness cycle on earth. Maintaining cellular activities in synchrony with the activities of the organism (such as eating and sleeping) helps different tissue and organ systems coordinate and optimize their performance. The full extent of the mechanisms by which cells maintain the clock are still under investigation, but involve a core set of clock genes that regulate large networks of gene transcription both by direct transcriptional activation/repression as well as the recruitment of proteins that modify chromatin states more broadly.

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The transcription factor, myocyte enhancer factor-2 (MEF2), is required for normal circadian behavior in ; however, its role in the mammalian circadian system has not been established. Of the four mammalian genes, is highly expressed in the suprachiasmatic nucleus (SCN) of the hypothalamus, a region critical for coordinating peripheral circadian clocks. Using both conventional and brain-specific KO () mouse lines, we demonstrate that MEF2D is essential for maintaining the length of the circadian free-running period of locomotor activity and normal sleep patterns in male mice.

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Several different potassium channels modulate the activity of sleep-promoting neurons in the Drosophila brain, but the regulation of these channels is not completely understood. A recent study (Kempf et al., Nature, 2019) found that one of the potassium channel subunits, Hyperkinetic, alters the firing properties of sleep-promoting neurons in response to NADPH oxidation.

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Chronic fatigue is a debilitating disorder with widespread consequences, but effective treatment strategies are lacking. Novel genetic mouse models of fatigue may prove invaluable for studying its underlying physiological mechanisms and for testing treatments and interventions. In a screen of voluntary wheel-running behavior in N-ethyl-N-nitrosourea mutagenized C57BL/6J mice, we discovered two lines with low body weights and aberrant wheel-running patterns suggestive of a fatigue phenotype.

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A major challenge in human genetics is the validation of pathogenicity of heterozygous missense variants. This problem is well-illustrated by PROKR2 variants associated with Isolated GnRH Deficiency (IGD). Homozygous, loss of function variants in PROKR2 was initially implicated in autosomal recessive IGD; however, most IGD-associated PROKR2 variants are heterozygous.

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Mice with severe combined immunodeficiency (SCID) lack functional T and B lymphocytes, and have impaired cognitive abilities. We assessed social behaviors in male SCID and C57BL/6 (B6) juvenile mice. In a social preference task, SCID mice spent more time than B6 mice investigating a novel adult male mouse.

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Sex differences in behavior are widespread and often caused by hormonal differences between the sexes. In addition to hormones, the composition and numbers of the sex chromosomes also affect a variety of sex differences. In humans, X-chromosome genes are implicated in neurobehavioral disorders (i.

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Sex chromosome genes directly influence sex differences in behavior. The discovery of the Sry gene on the Y chromosome (Gubbay et al., 1990; Koopman et al.

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It is well known that genes and environment interact to produce behavioral phenotypes. One environmental factor with long-term effects on gene transcription and behavior is maternal care. A classic paradigm for examining maternal care and genetic interactions is to foster pups of one genetic strain to dams of a different strain ("between-strain fostering").

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Sex differences in the brain and behavior are primarily attributed to dichotomous androgen exposure between males and females during neonatal development, as well as adult responses to gonadal hormones. Here we tested an alternative hypothesis and asked if sex chromosome complement influences male copulatory behavior, a standard behavior for studies of sexual differentiation. We used two mouse models with non-canonical associations between chromosomal and gonadal sex.

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Bisphenol-A (BPA) is a component of polycarbonate resins, and, lately, concern has been raised about its potential negative effects on human health. BPA is an estrogen analog and, in addition, it can act as a DNA hypomethylator. We examined the effects of gestational exposure to BPA on several behaviors in C57BL/6J mice.

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