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801.
Japaridze T Senda A Nozaki H Yanagida M Suzuki T Ganzorig K Kushi Y Kida K Urashima T Bruckmaier RM Fukuda K 《Bioscience, biotechnology, and biochemistry》2012,76(4):712-720
A bovine lipocalin, previously identified as a putative odorant-binding protein in bovine colostrum (bcOBP), was cloned and expressed, and its monoclonal antibody was established. bcOBP was constantly secreted into milk on day of parturition until at least 10 d postpartum at a concentration of 181±39 μg/L. Besides milk, bcOBP occurred in the nasal mucus, saliva, amniotic fluid, vaginal discharge, and blood plasma. Despite its low concentration, the distribution pattern and the finding that bcOBP harbored a characteristic sequence motif, CxxxC, which is conserved among insect and mammal pheromone binding proteins, suggest that bcOBP functions as a pheromone carrier. The presence of bcOBP in the plasma at varied concentrations depending on the lactation period does not exclude the possibility that bcOBP is secreted into milk from the blood. Cross-reactivity of the monoclonal antibody indicated presence of proteins homologous to bcOBP in the colostrum of farm animals of Cetartiodactyla. 相似文献
802.
Matthew M. Meredith Erin M. Parry Justin A. Guay Nicholas O. Markham G. Russell Danner Keith A. Johnson Tamar Barkay Frank A. Fekete 《Current microbiology》2012,65(5):575-582
Twenty-nine bacterial isolates representing eight genera from the gastrointestinal tracts of feral brook trout Salvelinus fontinalis (Mitchell) demonstrated multiple maximal antibiotic resistances and concomitant broad-spectrum mercury (Hg) resistance. Equivalent viable plate counts on tryptic soy agar supplemented with either 0 or 25?μM HgCl2 verified the ubiquity of mercury resistance in this microbial environment. Mercury levels in lake water samples measured 1.5?ng?L?1; mercury concentrations in fish filets ranged from 81.8 to 1,080?ng?g?1 and correlated with fish length. The presence of similar antibiotic and Hg resistance patterns in multiple genera of gastrointestinal microflora supports a growing body of research that multiple selective genes can be transferred horizontally in the presence of an unrelated individual selective pressure. We present data that bioaccumulation of non-point source Hg pollution could be a selective pressure to accumulate both antibiotic and Hg resistant bacteria. 相似文献
803.
Hydra and its fellow cnidarians - sea anemones, corals and jellyfish - are simple, mostly sessile animals that depend on bioactive chemicals for survival. In this review, we briefly describe what is known about the chemical armament of Hydra, and detail future research directions where Hydra can help illuminate major questions in chemical ecology, pharmacology, developmental biology and evolution. Focusing on two groups of putative toxins from Hydra - phospholipase A2s and proteins containing ShK and zinc metalloprotease domains, we ask: how do different venom components act together during prey paralysis? How is a venom arsenal created and how does it evolve? How is the chemical arsenal delivered to its target? To what extent does a chemical and biotic coupling exist between an organism and its environment? We propose a model whereby in Hydra and other cnidarians, bioactive compounds are secreted both as localized point sources (nematocyte discharges) and across extensive body surfaces, likely combining to create complex "chemical landscapes". We speculate that these cnidarian-derived chemical landscapes may affect the surrounding community on scales from microns to, in the case of coral reefs, hundreds of kilometers. 相似文献
804.
Tamar Makov Tomer Fishman Marian R. Chertow Vered Blass 《Journal of Industrial Ecology》2019,23(3):549-559
Reuse via secondhand markets can extend the use phase of products, thereby reducing environmental impacts. Analyzing 500,000 listings of used Apple and Samsung smartphones sold in 2015 and 2016 via eBay, we examine which product properties affect how long smartphones retain market value and facilitate market‐based reuse. Our results suggest that although repairability and large memory size are typically thought to be “life extending,” in practice they have limited impact on the current economic life span of smartphones and their market‐based reuse. In contrast, we show that brand, an intangible product property, can extend smartphones’ economic life span by 12.5 months. Because longer economic life spans imply extended use phases and longer life spans overall, these results illustrate the potential of harnessing the intangible properties of products to promote sustainable consumption. 相似文献
805.
Allyson K. Palmer Ming Xu Yi Zhu Tamar Pirtskhalava Megan M. Weivoda Christine M. Hachfeld Larissa G. Prata Theo H. van Dijk Esther Verkade Grace Casaclang‐Verzosa Kurt O. Johnson Hajrunisa Cubro Ewald J. Doornebal Mikolaj Ogrodnik Diana Jurk Michael D. Jensen Eduardo N. Chini Jordan D. Miller Aleksey Matveyenko Michael B. Stout Marissa J. Schafer Thomas A. White LaTonya J. Hickson Marco Demaria Vesna Garovic Joseph Grande Edgar A. Arriaga Folkert Kuipers Thomas von Zglinicki Nathan K. LeBrasseur Judith Campisi Tamar Tchkonia James L. Kirkland 《Aging cell》2019,18(3)
Adipose tissue inflammation and dysfunction are associated with obesity‐related insulin resistance and diabetes, but mechanisms underlying this relationship are unclear. Although senescent cells accumulate in adipose tissue of obese humans and rodents, a direct pathogenic role for these cells in the development of diabetes remains to be demonstrated. Here, we show that reducing senescent cell burden in obese mice, either by activating drug‐inducible “suicide” genes driven by the p16Ink4a promoter or by treatment with senolytic agents, alleviates metabolic and adipose tissue dysfunction. These senolytic interventions improved glucose tolerance, enhanced insulin sensitivity, lowered circulating inflammatory mediators, and promoted adipogenesis in obese mice. Elimination of senescent cells also prevented the migration of transplanted monocytes into intra‐abdominal adipose tissue and reduced the number of macrophages in this tissue. In addition, microalbuminuria, renal podocyte function, and cardiac diastolic function improved with senolytic therapy. Our results implicate cellular senescence as a causal factor in obesity‐related inflammation and metabolic derangements and show that emerging senolytic agents hold promise for treating obesity‐related metabolic dysfunction and its complications. 相似文献
806.
807.
Type 1 Usher syndrome (USH1) is a recessively inherited condition, characterized by profound prelingual deafness, vestibular
areflexia, and prepubertal onset of retinitis pigmentosa (RP). While the auditory component of USH1 can be treated by cochlear
implants, to date there is no effective treatment for RP. USH1 can be caused by mutations in each of at least six genes. While
truncating mutations of these genes cause USH1, some missense mutations of the same genes cause nonsyndromic deafness. These
observations suggest that partial or low level activity of the encoded proteins may be sufficient for normal retinal function,
although not for normal hearing. In individuals with USH1 due to nonsense mutations, interventions enabling partial translation
of a full-length functional protein may delay the onset and/or progression of RP. One such possible therapeutic approach is
suppression of nonsense mutations by small molecules such as aminoglycosides. We decided to test this approach as a potential
therapy for RP in USH1 patients due to nonsense mutations. We initially focused on nonsense mutations of the PCDH15 gene, underlying USH1F. Here, we show suppression of several PCDH15 nonsense mutations, both in vitro and ex vivo. Suppression was achieved both by commercial aminoglycosides and by NB30, a
new aminoglycoside-derivative developed by us. NB30 has reduced cytotoxicity in comparison to commercial aminoglycosides,
and thus may be more efficiently used for therapeutic purposes. The research described here has important implications for
the development of targeted interventions that are effective for patients with USH1 caused by various nonsense mutations.
Annie Rebibo-Sabbah and Igor Nudelman contributed equally to this work. 相似文献
808.
With the rapid rate of COVID-19 infections and deaths, treatments and cures besides hand washing, social distancing, masks, isolation, and quarantines are urgently needed. The treatments and vaccines rely on the basic biophysics of the complex viral apparatus. Although proteins are serving as main drug and vaccine targets, therapeutic approaches targeting the 30,000 nucleotide RNA viral genome form important complementary approaches. Indeed, the high conservation of the viral genome, its close evolutionary relationship to other viruses, and the rise of gene editing and RNA-based vaccines all argue for a focus on the RNA agent itself. One of the key steps in the viral replication cycle inside host cells is the ribosomal frameshifting required for translation of overlapping open reading frames. The RNA frameshifting element (FSE), one of three highly conserved regions of coronaviruses, is believed to include a pseudoknot considered essential for this ribosomal switching. In this work, we apply our graph-theory-based framework for representing RNA secondary structures, “RAG (or RNA-As-Graphs),” to alter key structural features of the FSE of the SARS-CoV-2 virus. Specifically, using RAG machinery of genetic algorithms for inverse folding adapted for RNA structures with pseudoknots, we computationally predict minimal mutations that destroy a structurally important stem and/or the pseudoknot of the FSE, potentially dismantling the virus against translation of the polyproteins. Our microsecond molecular dynamics simulations of mutant structures indicate relatively stable secondary structures. These findings not only advance our computational design of RNAs containing pseudoknots, they pinpoint key residues of the SARS-CoV-2 virus as targets for antiviral drugs and gene editing approaches. 相似文献
809.
810.
Anna Brestovitsky Keren Nebenzahl-Sharon Peter Kechker Rakefet Sharf Tamar Kleinberger 《PLoS pathogens》2016,12(2)
The DNA damage response (DDR) is a conglomerate of pathways designed to detect DNA damage and signal its presence to cell cycle checkpoints and to the repair machinery, allowing the cell to pause and mend the damage, or if the damage is too severe, to trigger apoptosis or senescence. Various DDR branches are regulated by kinases of the phosphatidylinositol 3-kinase-like protein kinase family, including ataxia-telangiectasia mutated (ATM) and ATM- and Rad3-related (ATR). Replication intermediates and linear double-stranded genomes of DNA viruses are perceived by the cell as DNA damage and activate the DDR. If allowed to operate, the DDR will stimulate ligation of viral genomes and will inhibit virus replication. To prevent this outcome, many DNA viruses evolved ways to limit the DDR. As part of its attack on the DDR, adenovirus utilizes various viral proteins to cause degradation of DDR proteins and to sequester the MRN damage sensor outside virus replication centers. Here we show that adenovirus evolved yet another novel mechanism to inhibit the DDR. The E4orf4 protein, together with its cellular partner PP2A, reduces phosphorylation of ATM and ATR substrates in virus-infected cells and in cells treated with DNA damaging drugs, and causes accumulation of damaged DNA in the drug-treated cells. ATM and ATR are not mutually required for inhibition of their signaling pathways by E4orf4. ATM and ATR deficiency as well as E4orf4 expression enhance infection efficiency. Furthermore, E4orf4, previously reported to induce cancer-specific cell death when expressed alone, sensitizes cells to killing by sub-lethal concentrations of DNA damaging drugs, likely because it inhibits DNA damage repair. These findings provide one explanation for the cancer-specificity of E4orf4-induced cell death as many cancers have DDR deficiencies leading to increased reliance on the remaining intact DDR pathways and to enhanced susceptibility to DDR inhibitors such as E4orf4. Thus DDR inhibition by E4orf4 contributes both to the efficiency of adenovirus replication and to the ability of E4orf4 to kill cancer cells. 相似文献