Matters select最新文献

{"title":"Aurora kinase inhibitors delay regeneration in <i>Stentor coeruleus</i> at an intermediate step.","authors":"Athena Lin,&nbsp;Diana Summers,&nbsp;Sarah B Reiff,&nbsp;Aaron R Tipton,&nbsp;Sindy K Tang,&nbsp;Wallace F Marshall","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The giant unicellular ciliate Stentor coeruleus can be cut into pieces and each piece will regenerate into a healthy, full-sized individual. The molecular mechanism for how Stentor regenerates is a complete mystery, however, the process of regeneration shows striking similarities to the process of cell division. On a morphological level, the process of creating a second mouth in division or a new oral apparatus in regeneration have the same steps and occur in the same order. On the transcriptional level, genes encoding elements of the cell division and cell cycle regulatory machinery, including Aurora kinases, are differentially expressed during regeneration. This suggests that there may be some common regulatory mechanisms involved in both regeneration and cell division. If the cell cycle machinery really does play a role in regeneration, then inhibition of proteins that regulate the timing of cell division may also affect the timing of regeneration in Stentor. Here we show that two well-characterized Aurora kinase A+B inhibitors that affect the timing of regeneration. ZM447439 slows down regeneration by at least one hour. PF03814735 completely suppresses regeneration until the drug is removed. Here we provide the first direct experimental evidence that Stentor may harness the cell division machinery to regulate the sequential process of regeneration.</p>","PeriodicalId":92936,"journal":{"name":"Matters select","volume":"6 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9674330/pdf/nihms-1847172.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40474932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endocrine, metabolic, and endocannabinoid correlates of obesity in rats exhibiting high anxiety-related behaviors","authors":"J. Vega-Torres, Priya Kalyan-Masih, D. Argueta, N. DiPatrizio, Johnny D. Figueroa","doi":"10.19185/MATTERS.201906000003","DOIUrl":"https://doi.org/10.19185/MATTERS.201906000003","url":null,"abstract":"Anxiety disorders are major risk factors for obesity. However, the mechanisms accounting for this susceptibility remain unclear. Animal models have proved to be useful tools for understanding the role of emotional functioning in the development and maintenance of metabolic alterations implicated in obesity. Here we sought to determine the predictive value of behavioral indices of anxiety for hormonal and metabolic imbalances in rats. Adult Lewis rats were screened on the elevated plus maze (EPM). K-means clustering was used to divide the rats into two groups based on their anxiety index in the EPM: low (LA) and high anxiety (HA) rats. This proxy of anxiety combines individual EPM parameters and accepted ratios into a single score. Four weeks later, we measured markers of endocrine and metabolic function. We found that r­elative to LA rats, the HA rats exhibited reduced latencies to exit a modified light-dark conflict test. Our results show that the HA rats displayed increased corticosterone levels when compared to LA rats. Furthermore, the HA rats weighed more and exhibited an enhanced glycemic response to exogenously administered glucose during the glucose tolerance test, indicating glucose intolerance. Notably, when compared to LA rats, the HA rats showed higher circulating levels of the endogenous cannabinoid, 2-arachidonoyl-sn-glycerol (2-AG). Together, these data indicate that patterns of emotional reactivity associated with anxiety may share common pathological pathways with metabolic complications implicated in obesity. Uncovering metabolic risk factors for anxiety disorders have the potential to strongly impact how we treat mental illnesses.","PeriodicalId":92936,"journal":{"name":"Matters select","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42085735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Threonine 3 regulates Serine 13/16 phosphorylation in the huntingtin exon 1","authors":"F. Herrera, Joana Branco-Santos, T. Outeiro","doi":"10.19185/MATTERS.201905000005","DOIUrl":"https://doi.org/10.19185/MATTERS.201905000005","url":null,"abstract":"","PeriodicalId":92936,"journal":{"name":"Matters select","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49383087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increased bone marrow adiposity in murine femoro-tibial epiphyses exposed to 30 days of microgravity","authors":"Jamie Endicott, J. Fitzgerald","doi":"10.19185/MATTERS.201904000010","DOIUrl":"https://doi.org/10.19185/MATTERS.201904000010","url":null,"abstract":"Bone marrow mesenchymal stem cell (BM-MSC) differentiation in long bones is sensitive to mechanical loading. Increased loading promotes osteogenesis and reduces adipogenesis while reduced loading tips MSC differentiation away from the bone formation in favor of adipogenesis. To examine the effects of the unloading on epiphyseal bone and adipocyte content, subchondral femoro-tibial bones isolated from mice flown for 30 days in microgravity were assessed for evidence of altered bone area and adipocyte number. Consistent with the known response of bone to microgravity, 30 days of spaceflight resulted in approximately 25% less subchondral bone area. Concurrently, 10-fold more adipocytes were present in the bone marrow cavities of femur and tibia in flight compared to ground control samples. These data support the hypothesis that biomechanical unloading promotes adipogenic differentiation and confirms earlier studies in rat vertebrae of increased adipogenesis during 14 days of microgravity. The potential long-term effects of increased bone marrow adipocyte formation on flight personnel health is unknown and warrants further investigation.","PeriodicalId":92936,"journal":{"name":"Matters select","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49240500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of a Four-day Spaceflight and Recombinant Human Growth Hormone on Cancellous Bone Microarchitecture in Femoral Head of Rapidly Growing Male Rats","authors":"R. Turner, R. T. Deyhle, A. Branscum, U. Iwaniec","doi":"10.19185/MATTERS.201903000006","DOIUrl":"https://doi.org/10.19185/MATTERS.201903000006","url":null,"abstract":"Spaceflight results in reduced bone accrual and muscle atrophy in growing rodents. Some studies suggest that the detrimental effects of spaceflight are due, in part, to impaired growth hormone (GH) signaling. An experiment flown aboard STS-41 (October 6–10, 1990) evaluated the efficacy of recombinant human growth hormone (rhGH) in ameliorating the detrimental effects of spaceflight on the musculoskeletal system in male Sprague Dawley rats. The rats were 39 days old at launch and sacrificed following the 4–day flight. Ground controls (n=11/treatment group) and flight animals (n=8/treatment group) were treated with rhGH or excipient delivered using osmotic pumps implanted subcutaneously one day prior to launch. For the present examination, cancellous bone in the femoral head was evaluated using X-ray microtomography (microcomputed tomography), a technology not available when the study was performed. Spaceflight resulted in lower cancellous bone volume fraction, connectivity density, trabecular thickness and trabecular number, and higher trabecular separation. rhGH had no independent effect on cancellous bone architecture and there were no spaceflight by rhGH interactions. These findings suggest that a short interval of microgravity during rapid growth was sufficient to reduce accrual of cancellous bone and alter bone microarchitecture at an important weight bearing skeletal site. Additionally, increasing growth hormone levels was ineffective in preventing cancellous osteopenia in flight animals and did not increase cancellous bone volume fraction in ground controls.","PeriodicalId":92936,"journal":{"name":"Matters select","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44385313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sleep pressure regulates mushroom body neural-glial interactions in Drosophila.","authors":"William M Vanderheyden,&nbsp;Hans P A Van Dongen,&nbsp;Marcos G Frank,&nbsp;Jason R Gerstner","doi":"10.19185/matters.201903000008","DOIUrl":"https://doi.org/10.19185/matters.201903000008","url":null,"abstract":"<p><p>Sleep is a behavior that exists broadly across animal phyla, from flies to humans, and is necessary for normal brain function. Recent studies in both vertebrates and invertebrates have suggested a role for glial cells in sleep regulatory processes. Changes in neural-glial interactions have been shown to be critical for synaptic plasticity and circuit function. Here, we wanted to test the hypothesis that changes in sleep pressure alters neural-glial interactions. In the fruit fly, <i>Drosophila melanogaster</i>, sleep is known to be regulated by mushroom body (MB) circuits. We used the technique GFP Reconstitution Across Synaptic Partners (GRASP) to test whether changes in sleep pressure affect neural-glial interactions between MB neurons and astrocytes, a specialized glial cell type known to regulate sleep in flies and mammals. The MB-astrocyte GRASP signal was reduced after 24 h of sleep deprivation, whereas the signal returned to baseline levels following 72 h of recovery. Social enrichment, which increases sleep drive, similarly reduced the MB-astrocyte GRASP signal. We did not observe any changes in the MB-astrocyte GRASP signal over time-of-day, or following paraquat exposure or starvation. These data suggest that changes in sleep pressure are linked to dynamic changes in neural-glial interactions between astrocytes and neuronal sleep circuits, which are not caused by normal rest-activity cycles or stressors.</p>","PeriodicalId":92936,"journal":{"name":"Matters select","volume":"2019 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6959203/pdf/nihms-1023589.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37544865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of chick Lefty2 asymmetric enhancer","authors":"A. T. Tavares, A. Jacinto, J. Belo","doi":"10.19185/MATTERS.201807000006","DOIUrl":"https://doi.org/10.19185/MATTERS.201807000006","url":null,"abstract":"Long before the detection of the first morphological asymmetry in the developing embryo, left-right patterning is established by a conserved feedback mechanism involving the TGF-β-like signaling molecule Nodal and its antagonist Lefty. The left-sided expression of Lefty in the lateral plate mesoderm is directly induced by Nodal signaling through the transcriptional activation of an asymmetric enhancer known as ASE, which has been found in mouse Lefty2, and in human LEFTY1 and LEFTY2 genes. Here we report the identification of a similar ASE enhancer in the cis-regulatory region of chick Lefty2 gene. This ASE sequence is able to activate reporter gene transcription in the left lateral plate mesoderm, and contains Nodal-responsive elements. Therefore, our findings suggest that Lefty2 expression may also be directly induced by Nodal signaling in the chick embryo. This hypothesis should be addressed in future functional studies. Introduction In vertebrates and in some higher invertebrates, the establishment of left-right patterning is directed by the Nodal signaling cascade, which involves the Transforming Growth Factor β-like molecule Nodal, its antagonists Cerberus/Dan and Lefty, and the transcription factor Pitx2 [1] [2] [3]. During early development, Nodal signaling directly activates the expression of Nodal itself, Lefty2 and Pitx2 in the left lateral plate mesoderm (LPM) [1]. This process is mediated by the transcription factor FoxH1, which recognizes conserved sequence motifs in the asymmetric enhancer (or ASE) of those genes [4] [5] [6] [7] [8]. Therefore, Nodal signaling is amplified by self-induction, but is also strictly limited in space and time due to the feedback inhibition by Lefty. In zebrafish, mouse and human, 2 Lefty genes have arisen by independent duplications [9] [6]. In the mouse embryo, Lefty1 is expressed in the midline (floor plate and notochord), where it prevents Nodal signaling from spreading to the right side, whereas Lefty2 is expressed in the left LPM, where it leads to the downregulation of Nodal signaling [1]. In the chick, however, a single Lefty gene has been identified, Lefty2, which is expressed in both the midline and the left LPM [10] [11] [12]. Although the role of Lefty2 as an inhibitor of Nodal signaling appears to be conserved in the chick embryo [13], it is currently unclear whether the expression of chick Lefty2 is also regulated by a Nodal-responsive enhancer. In the present study, we addressed this question by investigating the presence of an ASE enhancer in the cis-regulatory region of chick Lefty2 gene. Objective To identify the cis-regulatory region of chick Lefty2 gene responsible for driving asymmetric expression in the left LPM. Identification of chick Lefty2 asymmetric enhancer DOI: 10.19185/matters.201807000006 Matters Select (ISSN: 2297-9239) | 2 a Figure Legend Figure 1. Characterization of chick Lefty2 left side-specific enhancer. (A) Sequence analysis of Lefty2 cis-regulatory region. The geno","PeriodicalId":92936,"journal":{"name":"Matters select","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43349951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The UNC-83/UNC-84 LINC members are required for body wall muscle nuclei positioning in C. elegans","authors":"A. Ofenbauer, B. Tursun","doi":"10.19185/MATTERS.201805000009","DOIUrl":"https://doi.org/10.19185/MATTERS.201805000009","url":null,"abstract":"From a mutagenesis screen in the nematode C. elegans we isolated the mutant bar18, showing an accumulation of muscle cell nuclei around the posterior pharyngeal bulb of the worm. Quantification of the overall amount of body wall muscle nuclei, based on the muscle-specific reporter myo-3p::gfp::NLS, revealed that the number of nuclei in bar18 mutants is unchanged compared to WT worms. The accumulation of muscle nuclei around the posterior pharyngeal bulb is due to a positioning defect, which can be precisely quantified by subdividing the worm into head, neck, and posterior body segments. Whole-genome sequencing revealed that bar18 animals carry a mutation in the KASHdomain gene unc-83 causing a premature STOP. An additional unc-83mutant allele recapitulates the phenotype, as does a mutant allele of UNC-84, a SUN-domain containing protein that interacts with UNC-83. UNC-83 and UNC-84 belong to a Linker of Nucleoskeleton and Cytoskeletonnuclear (LINC) complex that bridges the nuclear lamina with the cytoskeleton. SUN and KASH domain proteins are conserved in mammals and mutations in the corresponding genes have been linked to cancer, autism, muscular dystrophy and other diseases. Additionally, LINC complexes that function in nuclear migration have also been identified in mammals. We were able to rescue the unc-83 mutant phenotype by expressing the WT gene under a muscle-specific (myo-3p) promoter, demonstrating that the effect is cell autonomous. Mutations in either unc-83 or unc-84 have previously been linked to nuclear migration defects in P cells, intestinal cells and hyp7 hypodermal precursors but not in muscles. Whether the mis-positioning of muscle nuclei is due to migration or anchoring defects still needs to be determined. Introduction Thenuclear lamina is connected to the cytoskeleton via different ‘Linker of Nucleoskeleton and Cytoskeleton’ (LINC) complexes with a variety of functions. LINC complexes are widely conserved over various phyla, which include organisms such as plants, slime molds, yeast, roundworms, fruit flies and mammals. LINC complexes cross the nuclear membrane and are composed of SUN and KASH domain-containing proteins, which interact in the perinuclear space between the inner and outer nuclear membrane. KASH proteins are located at the outer nuclear membrane and may interact with actin filaments, microtubules (via dynein and kinesin), intermediate filaments (via spectrin), centrosomes and other cytoplasmic organelles. SUN proteins are located at the inner nuclear membrane and are associated with both chromatin and nuclear lamins. Functions include nuclear movement and anchoring, moving meiotic chromosomes and telomeres and sensing mechanic stimuli [1] [2] [3]. The KASH protein UNC-83 and the SUN protein UNC-84 form a LINC complex in C. elegans, which is required for migration of nuclei in P cells, intestinal cells and hyp7 hypodermal precursors, by recruiting dynein and kinesin-1 to the nuclear surface [4] [5] [6] [7] [8]","PeriodicalId":92936,"journal":{"name":"Matters select","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41623465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhanced plasticity of mature granule cells reduces survival of newborn neurons in the adult mouse hippocampus.","authors":"Felix B Kleine Borgmann,&nbsp;Johannes Gräff,&nbsp;Isabelle M Mansuy,&nbsp;Nicolas Toni,&nbsp;Sebastian Jessberger","doi":"10.19185/matters.201610000014","DOIUrl":"https://doi.org/10.19185/matters.201610000014","url":null,"abstract":"<p><p>Dentate granule cells are born throughout life in the mammalian hippocampus. The integration of newborn neurons into the dentate circuit is activity-dependent, and structural data characterizing synapse formation suggested that the survival of adult-born granule cells is regulated by competition for synaptic partners. Here we tested this hypothesis by using a mouse model with genetically enhanced plasticity of mature granule cells through temporally controlled expression of a nuclear inhibitor of protein phosphatase ₁ (NIPP₁*). Using thymidine analogues and retrovirus-mediated cell labeling, we show that synaptic integration and subsequent survival of newborn neurons is decreased in NIPP₁*-expressing mice, suggesting that newborn neurons compete with preexisting granule cells for stable integration. The data presented here provides experimental evidence for a long-standing hypothesis and suggest cellular competition as a key mechanism regulating the integration and survival of newborn granule cells in the adult mammalian hippocampus.</p>","PeriodicalId":92936,"journal":{"name":"Matters select","volume":"2 12","pages":"201610000014"},"PeriodicalIF":0.0,"publicationDate":"2016-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7613637/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40379982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}