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Ramy K A Sayed, Marisol Fernández-Ortiz, María E Diaz-Casado, Iryna Rusanova, Ibtissem Rahim, Germaine Escames, Luis C López, Doaa M Mokhtar, Darío Acuña-Castroviejo
To gain insight into the mechanism of sarcopenia and the protective effect of melatonin, the gastrocnemius muscles of young (3-4 months), early-aged (12 months), and old-aged (24 months) wild type C57BL/6J female mice, were examined by magnetic resonance and microscopy. Locomotor activity, lactate production and nuclear apoptosis were also assessed. The results support the early onset of sarcopenia at 12 months of age, with reduction of muscle fibers' number, muscle weight/body weight ratio, lactate, and locomotor activity...
March 19, 2018: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
Patrick J Short, Jeremy F McRae, Giuseppe Gallone, Alejandro Sifrim, Hyejung Won, Daniel H Geschwind, Caroline F Wright, Helen V Firth, David R FitzPatrick, Jeffrey C Barrett, Matthew E Hurles
We previously estimated that 42% of patients with severe developmental disorders carry pathogenic de novo mutations in coding sequences. The role of de novo mutations in regulatory elements affecting genes associated with developmental disorders, or other genes, has been essentially unexplored. We identified de novo mutations in three classes of putative regulatory elements in almost 8,000 patients with developmental disorders. Here we show that de novo mutations in highly evolutionarily conserved fetal brain-active elements are significantly and specifically enriched in neurodevelopmental disorders...
March 21, 2018: Nature
Andrew C Peifer, Patrick H Maxwell
Retrotransposons are abundant mobile DNA elements in eukaryotic genomes that are more active with age in diverse species. Details of the regulation and consequences of retrotransposon activity during aging remain to be determined. Ty1 retromobility in Saccharomyces cerevisiae is more frequent in mother cells compared to daughter cells, and we found that Ty1 was more mobile in nonquiescent compared to quiescent subpopulations of stationary phase cells. This retromobility asymmetry was absent in mutant strains lacking BRP1 that have reduced expression of the essential Pma1p plasma membrane proton pump, lacking the mRNA decay gene LSM1 , and in cells exposed to a high concentration of calcium...
March 21, 2018: Aging
György Abrusán, Joseph A Marsh
It has been suggested that the evolution of protein complexes is significantly influenced by stochastic, non-adaptive processes. Using ligand binding as a proxy of function, we show that the structure of ligand-binding sites significantly influences the evolution of protein complexes. We show that homomers with multi-chain binding sites (MBSs) evolve new functions slower than monomers or other homomers, and those binding cofactors and metals have more conserved quaternary structure than other homomers. Moreover, the ligands and ligand-binding pockets of homologous MBS homomers are more similar than monomers and other homomers...
March 20, 2018: Cell Reports
Kathrin Theil, Margareta Herzog, Nikolaus Rajewsky
In mRNA sequences, 3' UTRs are thought to contain most elements that specifically regulate localization, turnover, and translation. Although high-throughput experiments indicate that many RNA-binding proteins (RBPs) also bind 5' UTRs, much less is known about specific post-transcriptional control exerted by 5' UTRs. GLD-1 is a conserved RBP and a translational repressor with essential roles in Caenorhabditis elegans germ cell development. Previously, we showed that GLD-1 binds highly conserved sites in both 3' and 5' UTRs...
March 20, 2018: Cell Reports
Tadashi Nomura, Wataru Yamashita, Hitoshi Gotoh, Katsuhiko Ono
Highly ordered brain architectures in vertebrates consist of multiple neuron subtypes with specific neuronal connections. However, the origin of and evolutionary changes in neuron specification mechanisms remain unclear. Here, we report that regulatory mechanisms of neuron subtype specification are divergent in developing amniote brains. In the mammalian neocortex, the transcription factors (TFs) Ctip2 and Satb2 are differentially expressed in layer-specific neurons. In contrast, these TFs are co-localized in reptilian and avian dorsal pallial neurons...
March 20, 2018: Cell Reports
Dacheng Ma, Shuguang Peng, Weiren Huang, Zhiming Cai, Zhen Xie
Nuclease dead Cas9 (dCas9) has been widely used for modulating gene expression by fusing with different activation or repression domains. However, delivery of the CRISPR/Cas system fused with variant effector domains in a single adeno-associated virus (AAV) remains challenging due to the payload limit. Here, we engineered a set of downsized variants of Cas9 including Staphylococcus aureus Cas9 (SaCas9) that retained DNA binding activity by deleting conserved functional domains. We demonstrated that fusing FokI nuclease domain to the N-terminal of the minimal SaCas9 (mini-SaCas9) or to the middle of the split mini-SaCas9 can trigger efficient DNA cleavage...
March 21, 2018: ACS Synthetic Biology
Elizabeth Bevan, Scott Whiting, Tony Tucker, Michael Guinea, Andrew Raith, Ryan Douglas
Drones are being increasingly used in innovative ways to enhance environmental research and conservation. Despite their widespread use for wildlife studies, there are few scientifically justified guidelines that provide minimum distances at which wildlife can be approached to minimize visual and auditory disturbance. These distances are essential to ensure that behavioral and survey data have no observer bias and form the basis of requirements for animal ethics and scientific permit approvals. In the present study, we documented the behaviors of three species of sea turtle (green turtles, Chelonia mydas, flatback turtles, Natator depressus, hawksbill turtles, Eretmochelys imbricata), saltwater crocodiles (Crocodylus porosus), and crested terns (Thalasseus bergii) in response to a small commercially available (1...
2018: PloS One
Bridget P Bannerman, Susanne Kramer, Richard G Dorrell, Mark Carrington
The degree of conservation and evolution of cytoplasmic mRNA metabolism pathways across the eukaryotes remains incompletely resolved. In this study, we describe a comprehensive genome and transcriptome-wide analysis of proteins involved in mRNA maturation, translation, and mRNA decay across representative organisms from the six eukaryotic super-groups. We demonstrate that eukaryotes share common pathways for mRNA metabolism that were almost certainly present in the last eukaryotic common ancestor, and show for the first time a correlation between intron density and a selective absence of some Exon Junction Complex (EJC) components in eukaryotes...
2018: PloS One
Kanchan Thapa, Sulochana Manandhar, Manisha Bista, Jivan Shakya, Govind Sah, Maheshwar Dhakal, Netra Sharma, Bronwyn Llewellyn, Claudia Wultsch, Lisette P Waits, Marcella J Kelly, Jean-Marc Hero, Jane Hughes, Dibesh Karmacharya
With fewer than 200 tigers (Panthera tigris tigris) left in Nepal, that are generally confined to five protected areas across the Terai Arc Landscape, genetic studies are needed to provide crucial information on diversity and connectivity for devising an effective country-wide tiger conservation strategy. As part of the Nepal Tiger Genome Project, we studied landscape change, genetic variation, population structure, and gene flow of tigers across the Terai Arc Landscape by conducting Nepal's first comprehensive and systematic scat-based, non-invasive genetic survey...
2018: PloS One
Gustavo Tejera, Beneharo Rodríguez, Carlos Armas, Airam Rodríguez
Insular wildlife is more prone to extinction than their mainland relatives. Thus, a basic understanding of non-natural mortality sources is the first step in the development of conservation management plans. The Canary Islands are an important tourist destination due to their unique climate and rich scenery and biodiversity. During the last few decades, there has been significant development of urban areas and busy road networks. However, there have been no studies describing the effects of road mortality on wildlife in this archipelago...
2018: PloS One
Joanna X Wu, Chad B Wilsey, Lotem Taylor, Gregor W Schuurman
Birds in U.S. national parks find strong protection from many longstanding and pervasive threats, but remain highly exposed to effects of ongoing climate change. To understand how climate change is likely to alter bird communities in parks, we used species distribution models relating North American Breeding Bird Survey (summer) and Audubon Christmas Bird Count (winter) observations to climate data from the early 2000s and projected to 2041-2070 (hereafter, mid-century) under high and low greenhouse gas concentration trajectories, RCP8...
2018: PloS One
Songzhen He, Xiaoling Tong, Minjin Han, Yanmin Bai, Fangyin Dai
The tyrosine kinases (TKs) are important parts of metazoan signaling pathways and play significant roles in cell growth, development, apoptosis and disease. Genome-wide characterization of TKs has been conducted in many metazoans, however, systematic information about this family in Lepidoptera is still lacking. We retrieved 33 TK-encoding genes in silkworm and classified them into 25 subfamilies by sequence analysis, without members in AXL, FRK, PDGFR, STYK1 and TIE subfamilies. Although domain sequences in each subfamily are conserved, TKs in vertebrates tend to be remarkably conserved and stable...
March 21, 2018: International Journal of Molecular Sciences
Ayako Casanova-Nakayama, Elena Wernicke von Siebenthal, Christian Kropf, Elisabeth Oldenberg, Helmut Segner
Genomic actions of estrogens in vertebrates are exerted via two intracellular estrogen receptor (ER) subtypes, ERα and ERβ, which show cell- and tissue-specific expression profiles. Mammalian immune cells express ERs and are responsive to estrogens. More recently, evidence became available that ERs are also present in the immune organs and cells of teleost fish, suggesting that the immunomodulatory function of estrogens has been conserved throughout vertebrate evolution. For a better understanding of the sensitivity and the responsiveness of the fish immune system to estrogens, more insight is needed on the abundance of ERs in the fish immune system, the cellular ratios of the ER subtypes, and their autoregulation by estrogens...
March 21, 2018: International Journal of Molecular Sciences
Eliel Ruiz-May, Iben Sørensen, Zhangjun Fei, Sheng Zhang, David S Domozych, Jocelyn K C Rose
The secretome can be defined as the population of proteins that are secreted into the extracellular environment. Many proteins that are secreted by eukaryotes are N -glycosylated. However, there are striking differences in the diversity and conservation of N -glycosylation patterns between taxa. For example, the secretome and N -glycosylation structures differ between land plants and chlorophyte green algae, but it is not clear when this divergence took place during plant evolution. A potentially valuable system to study this issue is provided by the charophycean green algae (CGA), which is the immediate ancestors of land plants...
March 21, 2018: Proteomes
Leigh Anne Harden, Jennifer Fernandez, Joseph R Milanovich, Brock P Struecker, Stephen R Midway
Blood biochemical and hematology analyses are helpful indicators of the physiologic health of animals, particularly when making conservation and management decisions for threatened species. In this study, we 1) established blood biochemical reference intervals for two populations of threatened, free-ranging ornate box turtles ( Terrapene ornata) in northern Illinois during their active season and 2) examined the effects of individual carapace temperature ( Tc ) on blood biochemical variables by using a Bayesian hierarchic framework...
March 21, 2018: Journal of Wildlife Diseases
Andrew VonHandorf, Francisco Javier Sánchez-Martín, Jacek Biesiada, Hongxia Zhang, Xiang Zhang, Mario Medvedovic, Alvaro Puga
Hexavalent chromium compounds are well-established respiratory carcinogens used in industrial processes. While inhalation exposure constitutes an occupational risk affecting mostly chromium workers, environmental exposure from drinking water is a widespread gastrointestinal cancer risk, affecting millions of people throughout the world. Cr(VI) is genotoxic, forming protein-Cr-DNA adducts and silencing tumor suppressor genes, but its mechanism of action at the molecular level is poorly understood. Our prior work using FAIRE showed that Cr(VI) disrupted the binding of transcription factors CTCF and AP-1 to their cognate chromatin sites...
March 21, 2018: Epigenetics: Official Journal of the DNA Methylation Society
Lei Lei, Kesava Phaneendra Cherukuri, Uria Alcolombri, Diana Meltzer, Dan S Tawfik
Marine organisms release dimethylsulfide (DMS) via cleavage of dimethylsulfoniopropionate (DMSP). Different genes encoding proteins with DMSP lyase activity are known, yet these exhibit highly variable levels of activity. Most assigned bacterial DMSP lyases, including DddK, DddL, DddQ, DddW and DddY, appear to belong to one, cupin-like superfamily. Here, we attempted to define and map this superfamily dubbed Cupin-DLL: DMSP lyases and lyase-like. To this end, we have pursued the characterization of various recombinant DMSP lyases belonging to this superfamily of metallo-enzymes, and especially of DddY and DddL that seem to be the most active DMSP lyases in this superfamily...
March 21, 2018: Biochemistry
Bo Ma, Yingjun Zhu, Yixin Liu
Atypical polypoid adenomyoma (APA) is a rare uterine lesion, which has a high rate of recurrence and malignant transformation. How to treat this disease is crucial for the prognosis, but there are few reports on it.We retrospectively reviewed the clinical records of all the patients diagnosed with APA after surgical therapy in our hospital. All the clinical information, pathological results, treatment, and outcome were retrieved from the clinical records.A total of 43 patients were diagnosed with APA. The median age was 56...
March 2018: Medicine (Baltimore)
Pradipta Ray, Andrew Torck, Lilyana Quigley, Andi Wangzhou, Matthew Neiman, Chandranshu Rao, Tiffany Lam, Ji-Young Kim, Tae Hoon Kim, Michael Q Zhang, Gregory Dussor, Theodore J Price
Molecular neurobiological insight into human nervous tissues is needed to generate next generation therapeutics for neurological disorders like chronic pain. We obtained human Dorsal Root Ganglia (DRG) samples from organ donors and performed RNA-sequencing (RNA-seq) to study the human DRG (hDRG) transcriptional landscape, systematically comparing it with publicly available data from a variety of human and orthologous mouse tissues, including mouse DRG (mDRG). We characterized the hDRG transcriptional profile in terms of tissue-restricted gene co-expression patterns and putative transcriptional regulators, and formulated an information-theoretic framework to quantify DRG enrichment...
March 20, 2018: Pain
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