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  • 1
    Publication Date: 2019
    Description: 〈p〉The posttranslational modification of histones is crucial in spermatogenesis, as in other tissues; however, during spermiogenesis, histones are replaced with protamines, which are critical for the tight packaging of the DNA in sperm cells. Protamines are also posttranslationally modified by phosphorylation and dephosphorylation, which prompted our investigation of the underlying mechanisms and biological consequences of their regulation. On the basis of a screen that implicated the heat shock protein Hspa4l in spermatogenesis, we generated mice deficient in Hspa4l (〈i〉Hspa4l〈/i〉-null mice), which showed male infertility and the malformation of sperm heads. These phenotypes are similar to those of 〈i〉Ppp1cc〈/i〉-deficient mice, and we found that the amount of a testis- and sperm-specific isoform of the Ppp1cc phosphatase (Ppp1cc2) in the chromatin-binding fraction was substantially less in 〈i〉Hspa4l〈/i〉-null spermatozoa than that in those of wild-type mice. We further showed that Ppp1cc2 was a substrate of the chaperones Hsc70 and Hsp70 and that Hspa4l enhanced the release of Ppp1cc2 from these complexes, enabling the freed Ppp1cc2 to localize to chromatin. Pull-down and in vitro phosphatase assays suggested the dephosphorylation of protamine 2 at serine 56 (Prm2 Ser〈sup〉56〈/sup〉) by Ppp1cc2. To confirm the biological importance of Prm2 Ser〈sup〉56〈/sup〉 dephosphorylation, we mutated Ser〈sup〉56〈/sup〉 to alanine in Prm2 (Prm2 S56A). Introduction of this mutation to 〈i〉Hspa4l〈/i〉-null mice (〈i〉Hspa4l〈/i〉〈sup〉–/–〈/sup〉; 〈i〉Prm2〈/i〉〈sup〉S56A/S56A〈/sup〉) restored the malformation of sperm heads and the infertility of 〈i〉Hspa4l〈/i〉〈sup〉–/–〈/sup〉 mice. The dephosphorylation signal to eliminate phosphate was crucial, and these results unveiled the mechanism and biological relevance of the dephosphorylation of Prm2 for sperm maturation in vivo.〈/p〉
    Print ISSN: 1945-0877
    Electronic ISSN: 1937-9145
    Topics: Biology , Medicine
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  • 2
    Publication Date: 2015-11-07
    Description: The sense of smell allows chemicals to be perceived as diverse scents. We used single-neuron RNA sequencing to explore the developmental mechanisms that shape this ability as nasal olfactory neurons mature in mice. Most mature neurons expressed only one of the ~1000 odorant receptor genes (Olfrs) available, and at a high level. However, many immature neurons expressed low levels of multiple Olfrs. Coexpressed Olfrs localized to overlapping zones of the nasal epithelium, suggesting regional biases, but not to single genomic loci. A single immature neuron could express Olfrs from up to seven different chromosomes. The mature state in which expression of Olfr genes is restricted to one per neuron emerges over a developmental progression that appears to be independent of neuronal activity involving sensory transduction molecules.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hanchate, Naresh K -- Kondoh, Kunio -- Lu, Zhonghua -- Kuang, Donghui -- Ye, Xiaolan -- Qiu, Xiaojie -- Pachter, Lior -- Trapnell, Cole -- Buck, Linda B -- DP2 HD088158/DP/NCCDPHP CDC HHS/ -- R01 DC009324/DC/NIDCD NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2015 Dec 4;350(6265):1251-5. doi: 10.1126/science.aad2456. Epub 2015 Nov 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Basic Sciences Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, WA 98109, USA. ; Department of Genome Sciences, University of Washington, Seattle, WA 98115, USA. Molecular and Cellular Biology Program, University of Washington, Seattle, WA 98115, USA. ; Departments of Mathematics, Molecular and Cell Biology, and Electrical Engineering and Computer Sciences, University of California-Berkeley, Berkeley, CA 94720, USA. ; Department of Genome Sciences, University of Washington, Seattle, WA 98115, USA. coletrap@uw.edu lbuck@fhcrc.org. ; Howard Hughes Medical Institute, Basic Sciences Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, WA 98109, USA. coletrap@uw.edu lbuck@fhcrc.org.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26541607" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Basic Helix-Loop-Helix Transcription Factors/genetics ; Cyclic Nucleotide-Gated Cation Channels/genetics ; *Gene Expression Regulation, Developmental ; Genetic Loci ; Genetic Markers ; Mice ; Mice, Inbred C57BL ; Neural Stem Cells/*metabolism ; Neurogenesis/*genetics ; Olfactory Mucosa/innervation ; Olfactory Receptor Neurons/*metabolism ; Receptors, Odorant/*genetics ; Sequence Analysis, RNA ; Single-Cell Analysis ; Smell/*genetics ; Transcriptome
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2016-03-24
    Description: Instinctive reactions to danger are critical to the perpetuation of species and are observed throughout the animal kingdom. The scent of predators induces an instinctive fear response in mice that includes behavioural changes, as well as a surge in blood stress hormones that mobilizes multiple body systems to escape impending danger. How the olfactory system routes predator signals detected in the nose to achieve these effects is unknown. Here we identify a specific area of the olfactory cortex in mice that induces stress hormone responses to volatile predator odours. Using monosynaptic and polysynaptic viral tracers, we found that multiple olfactory cortical areas transmit signals to hypothalamic corticotropin-releasing hormone (CRH) neurons, which control stress hormone levels. However, only one minor cortical area, the amygdalo-piriform transition area (AmPir), contained neurons upstream of CRH neurons that were activated by volatile predator odours. Chemogenetic stimulation of AmPir activated CRH neurons and induced an increase in blood stress hormones, mimicking an instinctive fear response. Moreover, chemogenetic silencing of AmPir markedly reduced the stress hormone response to predator odours without affecting a fear behaviour. These findings suggest that AmPir, a small area comprising 〈5% of the olfactory cortex, plays a key part in the hormonal component of the instinctive fear response to volatile predator scents.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kondoh, Kunio -- Lu, Zhonghua -- Ye, Xiaolan -- Olson, David P -- Lowell, Bradford B -- Buck, Linda B -- Howard Hughes Medical Institute/ -- England -- Nature. 2016 Apr 7;532(7597):103-6. doi: 10.1038/nature17156. Epub 2016 Mar 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Basic Sciences Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, Washington 98109, USA. ; Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27001694" target="_blank"〉PubMed〈/a〉
    Keywords: Adrenocorticotropic Hormone/blood ; Animals ; Corticosterone/blood ; Corticotropin-Releasing Hormone/blood/metabolism ; Escape Reaction ; Fear ; Female ; Hippocampus/cytology/physiology ; Hormones/blood/*metabolism ; Instinct ; Male ; Mice ; Neurons/metabolism ; Odors/*analysis ; Olfactory Cortex/*anatomy & histology/cytology/*physiology ; *Olfactory Pathways ; Olfactory Perception/physiology ; *Predatory Behavior ; Smell/*physiology ; *Stress, Psychological ; Telencephalon/anatomy & histology/cytology/physiology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 4
    Electronic Resource
    Electronic Resource
    [S.l.] : American Institute of Physics (AIP)
    Physics of Plasmas 8 (2001), S. 1545-1552 
    ISSN: 1089-7674
    Source: AIP Digital Archive
    Topics: Physics
    Notes: The spontaneous fast reconnection evolution is studied in a long current sheet system in various physical situations, where the threshold of current-driven anomalous resistivity is assumed to increase with the thermal velocity. If the initial threshold VC0 is sufficiently large in a low-β plasma, the fast reconnection mechanism can fully be set up; on the other hand, if VC0 is so small that the anomalous resistivity can easily occur in the usual circumstances, the resulting diffusion region notably lengthens so that the reconnection process becomes much less effective. Also, the fast reconnection evolution is strongly influenced by plasma β in the ambient magnetic field region, and an essential condition for the fast reconnection mechanism to evolve explosively is that the plasma β is sufficiently small. In fact, only in a low-β plasma does the magnetic tension force involved play the dominant role in the overall system dynamics and in the drastic magnetic energy release. It is also demonstrated that the fast reconnection evolution does not depend on the detailed functional form of the (current-driven) anomalous resistivity model. This is because the positive feedback between the anomalous resistivity and the reconnection flow effectively works so long as an anomalous resistivity is assumed to increase with the relative electron-ion drift velocity. © 2001 American Institute of Physics.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Biochemical and Biophysical Research Communications 181 (1991), S. 286-292 
    ISSN: 0006-291X
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Physics
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Biochemical and Biophysical Research Communications 204 (1994), S. 1352-1357 
    ISSN: 0006-291X
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Physics
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Biochemical and Biophysical Research Communications 176 (1991), S. 668-674 
    ISSN: 0006-291X
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Physics
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Biochemical and Biophysical Research Communications 204 (1994), S. 994-1000 
    ISSN: 0006-291X
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Physics
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Biochemical and Biophysical Research Communications 176 (1991), S. 668-674 
    ISSN: 0006-291X
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Physics
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Biochemical and Biophysical Research Communications 181 (1991), S. 286-292 
    ISSN: 0006-291X
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Physics
    Type of Medium: Electronic Resource
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