Plastic and Reconstructive Surgery Global Open, 2016
INtROdUCtION: Congenital syndactyly occurs in isolated and syndromic forms; method of reconstruct... more INtROdUCtION: Congenital syndactyly occurs in isolated and syndromic forms; method of reconstruction must be tailored to the type of syndactyly and postoperative function will depend on the preoperative state of the hand in addition to the method of reconstruction selected. We present the 18 year experience of surgical reconstruction of congenital syndactyly in all of its forms at a high throughput children’s hospital.
The maize (Zea mays) RNA Polymerase IV (Pol IV) largest subunit, RNA Polymerase D1 (RPD1 or NRPD1... more The maize (Zea mays) RNA Polymerase IV (Pol IV) largest subunit, RNA Polymerase D1 (RPD1 or NRPD1), is required for facilitating paramutations, restricting expression patterns of genes required for normal development, and generating small interfering RNA (siRNAs). Despite this expanded role for maize Pol IV relative to Arabidopsis thaliana, neither the general characteristics of Pol IV–regulated haplotypes, nor their prevalence, are known. Here, we show that specific haplotypes of the purple plant1 locus, encoding an anthocyanin pigment regulator, acquire and retain an expanded expression domain following transmission from siRNA biogenesis mutants. This conditioned expression pattern is progressively enhanced over generations in Pol IV mutants and then remains heritable after restoration of Pol IV function. This unusual genetic behavior is associated with promoter-proximal transposon fragments but is independent of sequences required for paramutation. These results indicate that tra...
Plants have distinct RNA polymerase complexes (Pol IV and Pol V) with largely unknown roles in ma... more Plants have distinct RNA polymerase complexes (Pol IV and Pol V) with largely unknown roles in maintaining small RNA–associated gene silencing. Curiously, the eudicot Arabidopsis thaliana is not affected when either function is lost. By use of mutation selection and positional cloning, we showed that the largest subunit of the presumed maize Pol IV is involved in paramutation, an inherited epigenetic change facilitated by an interaction between two alleles, as well as normal maize development. Bioinformatics analyses and nuclear run-on transcription assays indicate that Pol IV does not engage in the efficient RNA synthesis typical of the three major eukaryotic DNA-dependent RNA polymerases. These results indicate that Pol IV employs abnormal RNA polymerase activities to achieve genome-wide silencing and that its absence affects both maize development and heritable epigenetic changes.
Neuronal signal transduction by the JNK MAP kinase pathway is altered by a broad array of stimuli... more Neuronal signal transduction by the JNK MAP kinase pathway is altered by a broad array of stimuli including exposure to the widely abused drug ethanol, but the behavioral relevance and the regulation of JNK signaling is unclear. Here we demonstrate that JNK signaling functions downstream of the Sterile20 kinase family gene tao/Taok3 to regulate the behavioral effects of acute ethanol exposure in both the fruit fly Drosophila and mice. In flies tao is required in neurons to promote sensitivity to the locomotor stimulant effects of acute ethanol exposure and to establish specific brain structures. Reduced expression of key JNK pathway genes substantially rescued the structural and behavioral phenotypes of tao mutants. Decreasing and increasing JNK pathway activity resulted in increased and decreased sensitivity to the locomotor stimulant properties of acute ethanol exposure, respectively. Further, JNK expression in a limited pattern of neurons that included brain regions implicated in...
It is textbook knowledge that inheritance of traits is governed by genetics, and that the epigene... more It is textbook knowledge that inheritance of traits is governed by genetics, and that the epigenetic modifications an organism acquires are largely reset between generations. Recently, however, transgenerational epigenetic inheritance has emerged as a rapidly growing field, providing evidence suggesting that some epigenetic changes result in persistent phenotypes across generations. Here, we survey some of the most recent examples of transgenerational epigenetic inheritance in animals, ranging from Caenorhabditis elegans to humans, and describe approaches and limitations to studying this phenomenon. We also review the current body of evidence implicating chromatin modifications and RNA molecules in mechanisms underlying this unconventional mode of inheritance and discuss its evolutionary implications. Unconventional mode of inheritance Heredity is overwhelmingly acknowledged to be governed by the laws of Gregor Mendel, with genes as the primary templates of inherited information. Ho...
Joy-El R. Barbour,a Irene T. Liao,b Jennifer L. Stonaker,b,1 Jana P. Lim,b,2 Clarissa C. Lee,b,3 ... more Joy-El R. Barbour,a Irene T. Liao,b Jennifer L. Stonaker,b,1 Jana P. Lim,b,2 Clarissa C. Lee,b,3 Susan E. Parkinson,b Jerry Kermicle,c Stacey A. Simon,d BlakeC.Meyers,d RosalindWilliams-Carrier,e Alice Barkan,e and JayB. Hollickb,4 a Department of Molecular and Cell Biology, University of California, Berkeley, California 94720-3200 bDepartment of Plant and Microbial Biology, University of California, Berkeley, California 94720-3102 c Laboratory of Genetics, University of Wisconsin, Madison, Wisconsin 53706 dDelaware Biotechnology Institute, University of Delaware, Newark, Delaware 19711 e Institute of Molecular Biology, University of Oregon, Eugene, Oregon 97403
International Journal of Noncommunicable Diseases, 2016
Today and every day, 3 billion people worldwide use open fires to cook meals with susceptibility ... more Today and every day, 3 billion people worldwide use open fires to cook meals with susceptibility for fire-related burns. Of all burn injuries that occur worldwide, approximately 50% affect the hands of the victims. As a result, there are millions of patients worldwide who require treatment for hand burn injuries. Proper treatment starts with reconstructive surgery and must be followed by long-term physical rehabilitation in order for patients to achieve full recovery. Of patients who can travel to the city for surgery, only a small fraction receives proper physical therapy due to economic and geographic factors. Thus, these patients are at high risk for developing burn scar contractures or recontractures, immobilizing their hands, and resulting in lifelong disability. Our innovative splint allows for at home physical rehabilitation so that patients can heal at their own pace and prevent contractures without multiple hospital visits.
The ability to adapt behavior to environmental fluctuations is critical for survival of organisms... more The ability to adapt behavior to environmental fluctuations is critical for survival of organisms ranging from invertebrates to mammals. Caenorhabditis elegans can learn to avoid sodium chloride when it is paired with starvation. This behavior is likely advantageous to avoid areas without food. While some genes have been implicated in this salt aversive learning behavior, critical genetic components, and the neural circuit in which they act, remain elusive. Here, we show that the sole worm ortholog of mammalian CaMKI/IV, CMK-1, is essential for salt aversive learning behavior in C. elegans . We find that CMK-1 acts in the primary salt-sensing ASE neurons to regulate this behavior. By characterizing the intracellular calcium dynamics in ASE neurons using microfluidics, we find that loss of cmk-1 leads to an altered pattern of sensory-evoked calcium responses that may underlie salt aversive learning. Our study implicates the conserved CaMKI/CMK-1 as an essential cell-autonomous regula...
The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 6, 2018
The ability to adapt behavior to environmental fluctuations is critical for survival of organisms... more The ability to adapt behavior to environmental fluctuations is critical for survival of organisms ranging from invertebrates to mammals. can learn to avoid sodium chloride when it is paired with starvation. This behavior may help animals avoid areas without food. While some genes have been implicated in this salt aversive learning behavior, critical genetic components, and the neural circuit in which they act, remain elusive. Here, we show that the sole worm ortholog of mammalian CaMKI/IV, CMK-1, is essential for salt aversive learning behavior in hermaphrodites. We find that CMK-1 acts in the primary salt-sensing ASE neurons to regulate this behavior. By characterizing the intracellular calcium dynamics in ASE neurons using microfluidics, we find that loss of has subtle effects on sensory-evoked calcium responses in ASE axons and their modulation by salt conditioning. Our study implicates the expression of the conserved CaMKI/CMK-1 in chemosensory neurons as a regulator of behavior...
Despite recent advances in the understanding of ethanol's biologi... more Despite recent advances in the understanding of ethanol's biological action, many of the molecular targets of ethanol and mechanisms behind ethanol's effect on behavior remain poorly understood. In an effort to identify novel genes, the products of which regulate behavioral responses to ethanol, we recently identified a mutation in the dtao gene that confers resistance to the locomotor stimulating effect of ethanol in Drosophila. dtao encodes a member of the Ste20 family of serine/threonine kinases implicated in MAP kinase signaling pathways. In this study, we report that conditional ablation of the mouse dtao homolog, Taok2, constitutively and specifically in the nervous system, results in strain-specific and overlapping alterations in ethanol-dependent behaviors. These data suggest a functional conservation of dtao and Taok2 in mediating ethanol's biological action and identify Taok2 as a putative candidate gene for ethanol use disorders in humans.
Plastic and Reconstructive Surgery Global Open, 2016
INtROdUCtION: Congenital syndactyly occurs in isolated and syndromic forms; method of reconstruct... more INtROdUCtION: Congenital syndactyly occurs in isolated and syndromic forms; method of reconstruction must be tailored to the type of syndactyly and postoperative function will depend on the preoperative state of the hand in addition to the method of reconstruction selected. We present the 18 year experience of surgical reconstruction of congenital syndactyly in all of its forms at a high throughput children’s hospital.
The maize (Zea mays) RNA Polymerase IV (Pol IV) largest subunit, RNA Polymerase D1 (RPD1 or NRPD1... more The maize (Zea mays) RNA Polymerase IV (Pol IV) largest subunit, RNA Polymerase D1 (RPD1 or NRPD1), is required for facilitating paramutations, restricting expression patterns of genes required for normal development, and generating small interfering RNA (siRNAs). Despite this expanded role for maize Pol IV relative to Arabidopsis thaliana, neither the general characteristics of Pol IV–regulated haplotypes, nor their prevalence, are known. Here, we show that specific haplotypes of the purple plant1 locus, encoding an anthocyanin pigment regulator, acquire and retain an expanded expression domain following transmission from siRNA biogenesis mutants. This conditioned expression pattern is progressively enhanced over generations in Pol IV mutants and then remains heritable after restoration of Pol IV function. This unusual genetic behavior is associated with promoter-proximal transposon fragments but is independent of sequences required for paramutation. These results indicate that tra...
Plants have distinct RNA polymerase complexes (Pol IV and Pol V) with largely unknown roles in ma... more Plants have distinct RNA polymerase complexes (Pol IV and Pol V) with largely unknown roles in maintaining small RNA–associated gene silencing. Curiously, the eudicot Arabidopsis thaliana is not affected when either function is lost. By use of mutation selection and positional cloning, we showed that the largest subunit of the presumed maize Pol IV is involved in paramutation, an inherited epigenetic change facilitated by an interaction between two alleles, as well as normal maize development. Bioinformatics analyses and nuclear run-on transcription assays indicate that Pol IV does not engage in the efficient RNA synthesis typical of the three major eukaryotic DNA-dependent RNA polymerases. These results indicate that Pol IV employs abnormal RNA polymerase activities to achieve genome-wide silencing and that its absence affects both maize development and heritable epigenetic changes.
Neuronal signal transduction by the JNK MAP kinase pathway is altered by a broad array of stimuli... more Neuronal signal transduction by the JNK MAP kinase pathway is altered by a broad array of stimuli including exposure to the widely abused drug ethanol, but the behavioral relevance and the regulation of JNK signaling is unclear. Here we demonstrate that JNK signaling functions downstream of the Sterile20 kinase family gene tao/Taok3 to regulate the behavioral effects of acute ethanol exposure in both the fruit fly Drosophila and mice. In flies tao is required in neurons to promote sensitivity to the locomotor stimulant effects of acute ethanol exposure and to establish specific brain structures. Reduced expression of key JNK pathway genes substantially rescued the structural and behavioral phenotypes of tao mutants. Decreasing and increasing JNK pathway activity resulted in increased and decreased sensitivity to the locomotor stimulant properties of acute ethanol exposure, respectively. Further, JNK expression in a limited pattern of neurons that included brain regions implicated in...
It is textbook knowledge that inheritance of traits is governed by genetics, and that the epigene... more It is textbook knowledge that inheritance of traits is governed by genetics, and that the epigenetic modifications an organism acquires are largely reset between generations. Recently, however, transgenerational epigenetic inheritance has emerged as a rapidly growing field, providing evidence suggesting that some epigenetic changes result in persistent phenotypes across generations. Here, we survey some of the most recent examples of transgenerational epigenetic inheritance in animals, ranging from Caenorhabditis elegans to humans, and describe approaches and limitations to studying this phenomenon. We also review the current body of evidence implicating chromatin modifications and RNA molecules in mechanisms underlying this unconventional mode of inheritance and discuss its evolutionary implications. Unconventional mode of inheritance Heredity is overwhelmingly acknowledged to be governed by the laws of Gregor Mendel, with genes as the primary templates of inherited information. Ho...
Joy-El R. Barbour,a Irene T. Liao,b Jennifer L. Stonaker,b,1 Jana P. Lim,b,2 Clarissa C. Lee,b,3 ... more Joy-El R. Barbour,a Irene T. Liao,b Jennifer L. Stonaker,b,1 Jana P. Lim,b,2 Clarissa C. Lee,b,3 Susan E. Parkinson,b Jerry Kermicle,c Stacey A. Simon,d BlakeC.Meyers,d RosalindWilliams-Carrier,e Alice Barkan,e and JayB. Hollickb,4 a Department of Molecular and Cell Biology, University of California, Berkeley, California 94720-3200 bDepartment of Plant and Microbial Biology, University of California, Berkeley, California 94720-3102 c Laboratory of Genetics, University of Wisconsin, Madison, Wisconsin 53706 dDelaware Biotechnology Institute, University of Delaware, Newark, Delaware 19711 e Institute of Molecular Biology, University of Oregon, Eugene, Oregon 97403
International Journal of Noncommunicable Diseases, 2016
Today and every day, 3 billion people worldwide use open fires to cook meals with susceptibility ... more Today and every day, 3 billion people worldwide use open fires to cook meals with susceptibility for fire-related burns. Of all burn injuries that occur worldwide, approximately 50% affect the hands of the victims. As a result, there are millions of patients worldwide who require treatment for hand burn injuries. Proper treatment starts with reconstructive surgery and must be followed by long-term physical rehabilitation in order for patients to achieve full recovery. Of patients who can travel to the city for surgery, only a small fraction receives proper physical therapy due to economic and geographic factors. Thus, these patients are at high risk for developing burn scar contractures or recontractures, immobilizing their hands, and resulting in lifelong disability. Our innovative splint allows for at home physical rehabilitation so that patients can heal at their own pace and prevent contractures without multiple hospital visits.
The ability to adapt behavior to environmental fluctuations is critical for survival of organisms... more The ability to adapt behavior to environmental fluctuations is critical for survival of organisms ranging from invertebrates to mammals. Caenorhabditis elegans can learn to avoid sodium chloride when it is paired with starvation. This behavior is likely advantageous to avoid areas without food. While some genes have been implicated in this salt aversive learning behavior, critical genetic components, and the neural circuit in which they act, remain elusive. Here, we show that the sole worm ortholog of mammalian CaMKI/IV, CMK-1, is essential for salt aversive learning behavior in C. elegans . We find that CMK-1 acts in the primary salt-sensing ASE neurons to regulate this behavior. By characterizing the intracellular calcium dynamics in ASE neurons using microfluidics, we find that loss of cmk-1 leads to an altered pattern of sensory-evoked calcium responses that may underlie salt aversive learning. Our study implicates the conserved CaMKI/CMK-1 as an essential cell-autonomous regula...
The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 6, 2018
The ability to adapt behavior to environmental fluctuations is critical for survival of organisms... more The ability to adapt behavior to environmental fluctuations is critical for survival of organisms ranging from invertebrates to mammals. can learn to avoid sodium chloride when it is paired with starvation. This behavior may help animals avoid areas without food. While some genes have been implicated in this salt aversive learning behavior, critical genetic components, and the neural circuit in which they act, remain elusive. Here, we show that the sole worm ortholog of mammalian CaMKI/IV, CMK-1, is essential for salt aversive learning behavior in hermaphrodites. We find that CMK-1 acts in the primary salt-sensing ASE neurons to regulate this behavior. By characterizing the intracellular calcium dynamics in ASE neurons using microfluidics, we find that loss of has subtle effects on sensory-evoked calcium responses in ASE axons and their modulation by salt conditioning. Our study implicates the expression of the conserved CaMKI/CMK-1 in chemosensory neurons as a regulator of behavior...
Despite recent advances in the understanding of ethanol's biologi... more Despite recent advances in the understanding of ethanol's biological action, many of the molecular targets of ethanol and mechanisms behind ethanol's effect on behavior remain poorly understood. In an effort to identify novel genes, the products of which regulate behavioral responses to ethanol, we recently identified a mutation in the dtao gene that confers resistance to the locomotor stimulating effect of ethanol in Drosophila. dtao encodes a member of the Ste20 family of serine/threonine kinases implicated in MAP kinase signaling pathways. In this study, we report that conditional ablation of the mouse dtao homolog, Taok2, constitutively and specifically in the nervous system, results in strain-specific and overlapping alterations in ethanol-dependent behaviors. These data suggest a functional conservation of dtao and Taok2 in mediating ethanol's biological action and identify Taok2 as a putative candidate gene for ethanol use disorders in humans.
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Papers by Jana Lim