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    Hormonal and environmental signals guiding stomatal development.
    BMC Biol 2018 Feb 20;16(1):21. Epub 2018 Feb 20.
    Howard Hughes Medical Institute and Department of Biology, University of Washington, Seattle, WA, 98195, USA.
    Stomata are pores on plant epidermis that facilitate gas exchange and water evaporation between plants and the environment. Given the central role of stomata in photosynthesis and water-use efficiency, two vital events for plant growth, stomatal development is tightly controlled by a diverse range of signals. A family of peptide hormones regulates stomatal patterning and differentiation. Read More

    A phosphoinositide map at the shoot apical meristem in Arabidopsis thaliana.
    BMC Biol 2018 Feb 7;16(1):20. Epub 2018 Feb 7.
    Laboratoire de Reproduction et Développement des Plantes, Université de Lyon, ENS de Lyon, UCBL, INRA, CNRS, 46 Allée d'Italie, 69364, Lyon, Cedex 07, France.
    Background: In plants, the shoot apical meristem (SAM) has two main functions, involving the production of all aerial organs on the one hand and self-maintenance on the other, allowing the production of organs during the entire post-embryonic life of the plant. Transcription factors, microRNA, hormones, peptides and forces have been involved in meristem function. Whereas phosphatidylinositol phosphates (PIPs) have been involved in almost all biological functions, including stem cell maintenance and organogenesis in animals, the processes in meristem biology to which PIPs contribute still need to be delineated. Read More

    Marked differences in tight junction composition and macromolecular permeability among different intestinal cell types.
    BMC Biol 2018 Feb 1;16(1):19. Epub 2018 Feb 1.
    Department of Pharmacology, Physiology and Neurosciences, New Jersey Medical School, Rutgers University, Newark, NJ, 07103, USA.
    Background: Mammalian small intestinal tight junctions (TJ) link epithelial cells to one another and function as a permselective barrier, strictly modulating the passage of ions and macromolecules through the pore and leak pathways, respectively, thereby preventing the absorption of harmful compounds and microbes while allowing regulated transport of nutrients and electrolytes. Small intestinal epithelial permeability is ascribed primarily to the properties of TJs between adjoining enterocytes (ENTs), because there is almost no information on TJ composition and the paracellular permeability of nonenterocyte cell types that constitute a small but significant fraction of the intestinal epithelia.

    Results: Here we directed murine intestinal crypts to form specialized organoids highly enriched in intestinal stem cells (ISCs), absorptive ENTs, secretory goblet cells, or Paneth cells. Read More

    Stress-induced reproductive arrest in Drosophila occurs through ETH deficiency-mediated suppression of oogenesis and ovulation.
    BMC Biol 2018 Jan 30;16(1):18. Epub 2018 Jan 30.
    Departments of Entomology and Cell Biology and Neuroscience, University of California, Riverside, CA, 92521, USA.
    Background: Environmental stressors induce changes in endocrine state, leading to energy re-allocation from reproduction to survival. Female Drosophila melanogaster respond to thermal and nutrient stressors by arresting egg production through elevation of the steroid hormone ecdysone. However, the mechanisms through which this reproductive arrest occurs are not well understood. Read More

    Q&A: Trash talk: disposal and remote degradation of neuronal garbage.
    BMC Biol 2018 Jan 30;16(1):17. Epub 2018 Jan 30.
    Department of Molecular Biology and Biochemistry, Rutgers, The State University of New Jersey, A232 Nelson Biological Laboratories, 604 Allison Road, Piscataway, NJ, 08855, USA.
    Caenorhabditis elegans neurons have recently been found to throw out cellular debris for remote degradation and/or storage, adding an "extracellular garbage elimination" option to known intracellular protein and organelle degradation pathways. This Q&A describes initial insights into the biology of seemingly selective protein and organelle elimination by challenged neurons, highlighting mysteries of how garbage is distinguished and sorted in the sending neuron, how the garbage-filled "exophers" appear to elicit degradative responses as they transit neighboring tissue, and how non-digestible materials get thrown out of cells again via processes that may be highly relevant to human neurodegenerative disease mechanisms. Read More

    Sox5 is involved in germ-cell regulation and sex determination in medaka following co-option of nested transposable elements.
    BMC Biol 2018 Jan 29;16(1):16. Epub 2018 Jan 29.
    Physiological Chemistry, Biocenter, University of Würzburg, 97074, Würzburg, Germany.
    Background: Sex determination relies on a hierarchically structured network of genes, and is one of the most plastic processes in evolution. The evolution of sex-determining genes within a network, by neo- or sub-functionalization, also requires the regulatory landscape to be rewired to accommodate these novel gene functions. We previously showed that in medaka fish, the regulatory landscape of the master male-determining gene dmrt1bY underwent a profound rearrangement, concomitantly with acquiring a dominant position within the sex-determining network. Read More

    Phylogenomics of the olive tree (Olea europaea) reveals the relative contribution of ancient allo- and autopolyploidization events.
    BMC Biol 2018 Jan 25;16(1):15. Epub 2018 Jan 25.
    Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr. Aiguader 88, Barcelona, 08003, Spain.
    Background: Polyploidization is one of the major evolutionary processes that shape eukaryotic genomes, being particularly common in plants. Polyploids can arise through direct genome doubling within a species (autopolyploidization) or through the merging of genomes from distinct species after hybridization (allopolyploidization). The relative contribution of both mechanisms in plant evolution is debated. Read More

    Two-step interphase microtubule disassembly aids spindle morphogenesis.
    BMC Biol 2018 Jan 23;16(1):14. Epub 2018 Jan 23.
    MRC Laboratory of Molecular Cell Biology and the IPLS, University College London, Gower Street, London, WC1E 6BT, UK.
    Background: Entry into mitosis triggers profound changes in cell shape and cytoskeletal organisation. Here, by studying microtubule remodelling in human flat mitotic cells, we identify a two-step process of interphase microtubule disassembly.

    Results: First, a microtubule-stabilising protein, Ensconsin/MAP7, is inactivated in prophase as a consequence of its phosphorylation downstream of Cdk1/cyclin B. Read More

    ADMP controls the size of Spemann's organizer through a network of self-regulating expansion-restriction signals.
    BMC Biol 2018 Jan 22;16(1):13. Epub 2018 Jan 22.
    Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, 91120, Israel.
    Background: The bone morphogenetic protein (BMP) signaling gradient is central for dorsoventral patterning in amphibian embryos. This gradient is established through the interaction of several BMPs and BMP antagonists and modulators, some secreted by Spemann's organizer, a cluster of cells coordinating embryonic development. Anti-dorsalizing morphogenetic protein (ADMP), a BMP-like transforming growth factor beta ligand, negatively affects the formation of the organizer, although it is robustly expressed within the organizer itself. Read More

    Alarm pheromone and kairomone detection via bitter taste receptors in the mouse Grueneberg ganglion.
    BMC Biol 2018 Jan 18;16(1):12. Epub 2018 Jan 18.
    Department of Pharmacology and Toxicology, Faculty of Biology and Medicine, University of Lausanne, Lausanne, CH-1011, Switzerland.
    Background: The mouse Grueneberg ganglion (GG) is an olfactory subsystem specialized in the detection of volatile heterocyclic compounds signalling danger. The signalling pathways transducing the danger signals are only beginning to be characterized.

    Results: Screening chemical libraries for compounds structurally resembling the already-identified GG ligands, we found a new category of chemicals previously identified as bitter tastants that initiated fear-related behaviours in mice depending on their volatility and evoked neuronal responses in mouse GG neurons. Read More

    Hsp70 at the membrane: driving protein translocation.
    BMC Biol 2018 Jan 17;16(1):11. Epub 2018 Jan 17.
    Department of Biochemistry, University of Wisconsin - Madison, 433 Babcock Drive, Madison, WI, 53706, USA.
    Efficient movement of proteins across membranes is required for cell health. The translocation process is particularly challenging when the channel in the membrane through which proteins must pass is narrow-such as those in the membranes of the endoplasmic reticulum and mitochondria. Hsp70 molecular chaperones play roles on both sides of these membranes, ensuring efficient translocation of proteins synthesized on cytosolic ribosomes into the interior of these organelles. Read More

    A live cell assay of GPCR coupling allows identification of optogenetic tools for controlling Go and Gi signaling.
    BMC Biol 2018 Jan 16;16(1):10. Epub 2018 Jan 16.
    University of Manchester, Manchester, UK.
    Background: Animal opsins are light-sensitive G-protein-coupled receptors (GPCRs) that enable optogenetic control over the major heterotrimeric G-protein signaling pathways in animal cells. As such, opsins have potential applications in both biomedical research and therapy. Selecting the opsin with the best balance of activity and selectivity for a given application requires knowing their ability to couple to a full range of relevant Gα subunits. Read More

    A genetically encoded Caindicator based on circularly permutated sea anemone red fluorescent protein eqFP578.
    BMC Biol 2018 Jan 16;16(1). Epub 2018 Jan 16.
    Department of Chemistry, University of Alberta, Edmonton, Alberta, T6G 2G2, Canada.
    Background: Genetically encoded calcium ion (Ca) indicators (GECIs) are indispensable tools for measuring Cadynamics and neuronal activities in vitro and in vivo. Red fluorescent protein (RFP)-based GECIs have inherent advantages relative to green fluorescent protein-based GECIs due to the longer wavelength light used for excitation. Longer wavelength light is associated with decreased phototoxicity and deeper penetration through tissue. Read More

    WorMachine: machine learning-based phenotypic analysis tool for worms.
    BMC Biol 2018 Jan 16;16(1). Epub 2018 Jan 16.
    Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel.
    Background: Caenorhabditis elegans nematodes are powerful model organisms, yet quantification of visible phenotypes is still often labor-intensive, biased, and error-prone. We developed WorMachine, a three-step MATLAB-based image analysis software that allows (1) automated identification of C. elegans worms, (2) extraction of morphological features and quantification of fluorescent signals, and (3) machine learning techniques for high-level analysis. Read More

    Will human influences on evolutionary dynamics in the wild pervade the Anthropocene?
    BMC Biol 2018 Jan 15;16(1). Epub 2018 Jan 15.
    Department of Biological Sciences, University of Alberta, Edmonton, AB, T6G 2E9, Canada.
    The five most pervasive anthropogenic threats to biodiversity are over-exploitation, habitat changes, climate change, invasive species, and pollution. Since all of these threats can affect intraspecific biodiversity-including genetic variation within populations-humans have the potential to induce contemporary microevolution in wild populations. We highlight recent empirical studies that have explored the effects of these anthropogenic threats to intraspecific biodiversity in the wild. Read More

    A role for endothelial nitric oxide synthase in intestinal stem cell proliferation and mesenchymal colorectal cancer.
    BMC Biol 2018 Jan 10;16(1). Epub 2018 Jan 10.
    Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), 14004 Avda Menéndez Pidal s/n, Córdoba, Spain.
    Background: Nitric oxide (NO) has been highlighted as an important agent in cancer-related events. Although the inducible nitric oxide synthase (iNOS) isoform has received most attention, recent studies in the literature indicate that the endothelial isoenzyme (eNOS) can also modulate different tumor processes including resistance, angiogenesis, invasion, and metastasis. However, the role of eNOS in cancer stem cell (CSC) biology and mesenchymal tumors is unknown. Read More

    De novo assembly of the complex genome of Nippostrongylus brasiliensis using MinION long reads.
    BMC Biol 2018 Jan 11;16(1). Epub 2018 Jan 11.
    Malaghan Institute of Medical Research, Wellington, New Zealand.
    Background: Eukaryotic genome assembly remains a challenge in part due to the prevalence of complex DNA repeats. This is a particularly acute problem for holocentric nematodes because of the large number of satellite DNA sequences found throughout their genomes. These have been recalcitrant to most genome sequencing methods. Read More

    PINK1 import regulation; a fine system to convey mitochondrial stress to the cytosol.
    BMC Biol 2018 Jan 10;16(1). Epub 2018 Jan 10.
    Biochemistry Section, Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, 20892, USA.
    Insights from inherited forms of parkinsonism suggest that insufficient mitophagy may be one etiology of the disease. PINK1/Parkin-dependent mitophagy, which helps maintain a healthy mitochondrial network, is initiated by activation of the PINK1 kinase specifically on damaged mitochondria. Recent investigation of this process reveals that import of PINK1 into mitochondria is regulated and yields a stress-sensing mechanism. Read More

    Pangenome analyses of the wheat pathogen Zymoseptoria tritici reveal the structural basis of a highly plastic eukaryotic genome.
    BMC Biol 2018 Jan 11;16(1). Epub 2018 Jan 11.
    Laboratory of Evolutionary Genetics, Institute of Biology, University of Neuchâtel, CH-2000, Neuchâtel, Switzerland.
    Background: Structural variation contributes substantially to polymorphism within species. Chromosomal rearrangements that impact genes can lead to functional variation among individuals and influence the expression of phenotypic traits. Genomes of fungal pathogens show substantial chromosomal polymorphism that can drive virulence evolution on host plants. Read More

    Systematic target function annotation of human transcription factors.
    BMC Biol 2018 Jan 10;16(1). Epub 2018 Jan 10.
    Department of Bioengineering, Stanford University, Stanford, CA, USA.
    Background: Transcription factors (TFs), the key players in transcriptional regulation, have attracted great experimental attention, yet the functions of most human TFs remain poorly understood. Recent capabilities in genome-wide protein binding profiling have stimulated systematic studies of the hierarchical organization of human gene regulatory network and DNA-binding specificity of TFs, shedding light on combinatorial gene regulation. We show here that these data also enable a systematic annotation of the biological functions and functional diversity of TFs. Read More

    Phthiocerol dimycocerosates promote access to the cytosol and intracellular burden of Mycobacterium tuberculosis in lymphatic endothelial cells.
    BMC Biol 2018 Jan 4;16(1). Epub 2018 Jan 4.
    The Francis Crick Institute, 1 Midland Road, London, NW1 1AT, UK.
    Background: Phthiocerol dimycocerosates (PDIM), glycolipids found on the outer surface of virulent members of the Mycobacterium tuberculosis (Mtb) complex, are a major contributing factor to the pathogenesis of Mtb. Myelocytic cells, such as macrophages and dendritic cells, are the primary hosts for Mtb after infection and previous studies have shown multiple roles for PDIM in supporting Mtb in these cells. However, Mtb can infect other cell types. Read More

    Memory retrieval in addiction: a role for miR-105-mediated regulation of D1 receptors in mPFC neurons projecting to the basolateral amygdala.
    BMC Biol 2017 Dec 27;15(1):128. Epub 2017 Dec 27.
    State Key Laboratory of Medical Neurobiology, Department of Neurology, Zhongshan Hospital, Collaborative Innovation Center for Brain Science, School of Basic Medical Sciences and Institutes of Brain Science, Fudan University, Shanghai, 200032, China.
    Background: Drug addiction is a chronic brain disorder characterized by the compulsive use of drugs. The study of chronic morphine-induced adaptation in the brain and its functional significance is of importance to understand the mechanism of morphine addiction. Previous studies have found a number of chronic morphine-induced adaptive changes at molecular levels in the brain. Read More

    Q&A: Friends (but sometimes foes) within: the complex evolutionary ecology of symbioses between host and microbes.
    BMC Biol 2017 Dec 27;15(1):126. Epub 2017 Dec 27.
    Institute of Integrative Biology, University of Liverpool, Crown Street, Liverpool, L69 7ZB, UK.
    Over the past decade, there has been a pronounced shift in the study of host-microbe associations, with recognition that many of these associations are beneficial, and often critical, for a diverse array of hosts. There may also be pronounced benefits for the microbes, though this is less well empirically understood. Significant progress has been made in understanding how ecology and evolution shape simple associations between hosts and one or a few microbial species, and this work can serve as a foundation to study the ecology and evolution of host associations with their often complex microbial communities (microbiomes). Read More

    The human microbiome in evolution.
    BMC Biol 2017 Dec 27;15(1):127. Epub 2017 Dec 27.
    Department of Pediatrics, University of California San Diego, La Jolla, CA, USA.
    The trillions of microbes living in the gut-the gut microbiota-play an important role in human biology and disease. While much has been done to explore its diversity, a full understanding of our microbiomes demands an evolutionary perspective. In this review, we compare microbiomes from human populations, placing them in the context of microbes from humanity's near and distant animal relatives. Read More

    The Toll pathway underlies host sexual dimorphism in resistance to both Gram-negative and Gram-positive bacteria in mated Drosophila.
    BMC Biol 2017 Dec 21;15(1):124. Epub 2017 Dec 21.
    Université Toulouse 3 Paul Sabatier, CNRS, ENFA, UMR5174 EDB (Laboratoire Évolution & Diversité Biologique), 118 route de Narbonne, F-31062, Toulouse, France.
    Background: Host sexual dimorphism is being increasingly recognized to generate strong differences in the outcome of infectious disease, but the mechanisms underlying immunological differences between males and females remain poorly characterized. Here, we used Drosophila melanogaster to assess and dissect sexual dimorphism in the innate response to systemic bacterial infection.

    Results: We demonstrated sexual dimorphism in susceptibility to infection by a broad spectrum of Gram-positive and Gram-negative bacteria. Read More

    An elevated plus-maze in mixed reality for studying human anxiety-related behavior.
    BMC Biol 2017 Dec 21;15(1):125. Epub 2017 Dec 21.
    Human Behavior Laboratory, Institute for Sex Research and Forensic Psychiatry, Center of Psychosocial Medicine, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Germany.
    Background: A dearth of laboratory tests to study actual human approach-avoidance behavior has complicated translational research on anxiety. The elevated plus-maze (EPM) is the gold standard to assess approach-avoidance behavior in rodents.

    Methods: Here, we translated the EPM to humans using mixed reality through a combination of virtual and real-world elements. Read More

    Q&A: Why use synchrotron x-ray tomography for multi-scale connectome mapping?
    BMC Biol 2017 Dec 21;15(1):122. Epub 2017 Dec 21.
    Institute of Physics, Academia Sinica, Nankang, Taipei, 11529, Taiwan.
    To understand how information flows and is used in the human brain, we must map neural structures at all levels, providing visualizations similar to those of Google Earth for continents, countries, cities, and streets. Unfortunately, the imaging and processing techniques currently used in connectomics projects cannot achieve complete mapping for the brains of large animals within the timespan of a typical research career. However, feasible improvements in x-ray imaging would change this situation. Read More

    Outer membrane protein folding from an energy landscape perspective.
    BMC Biol 2017 Dec 21;15(1):123. Epub 2017 Dec 21.
    Astbury Centre for Structural Molecular Biology, School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, LS2 9JT, UK.
    The cell envelope is essential for the survival of Gram-negative bacteria. This specialised membrane is densely packed with outer membrane proteins (OMPs), which perform a variety of functions. How OMPs fold into this crowded environment remains an open question. Read More

    Investigating the physiology of viable but non-culturable bacteria by microfluidics and time-lapse microscopy.
    BMC Biol 2017 Dec 21;15(1):121. Epub 2017 Dec 21.
    Biosciences, University of Exeter, Exeter, Devon, EX4 4QD, UK.
    Background: Clonal microbial populations often harbor rare phenotypic variants that are typically hidden within the majority of the remaining cells, but are crucial for the population's resilience to external perturbations. Persister and viable but non-culturable (VBNC) cells are two important clonal bacterial subpopulations that can survive antibiotic treatment. Both persister and VBNC cells pose a serious threat to human health. Read More

    To Mia or not to Mia: stepwise evolution of the mitochondrial intermembrane space disulfide relay.
    BMC Biol 2017 Dec 14;15(1):119. Epub 2017 Dec 14.
    Department of Biology I, Botany, Ludwig-Maximilians-Universität München, Großhaderner Strasse 2-4, D-82152, Planegg-Martinsried, Germany.
    The disulfide relay system found in the intermembrane space (IMS) of mitochondria is an essential pathway for the import and oxidative folding of IMS proteins. Erv1, an essential member of this pathway, has been previously found to be ubiquitously present in mitochondria-containing eukaryotes. However, the other essential protein, Mia40, was found to be absent or not required in some organisms, raising questions about how the disulfide relay functions in these organisms. Read More

    Bile acid is a significant host factor shaping the gut microbiome of diet-induced obese mice.
    BMC Biol 2017 Dec 14;15(1):120. Epub 2017 Dec 14.
    Shanghai Key Laboratory of Diabetes Mellitus and Center for Translational Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Rd, Shanghai, 200233, China.
    Background: Intestinal bacteria are known to regulate bile acid (BA) homeostasis via intestinal biotransformation of BAs and stimulation of the expression of fibroblast growth factor 19 through intestinal nuclear farnesoid X receptor (FXR). On the other hand, BAs directly regulate the gut microbiota with their strong antimicrobial activities. It remains unclear, however, how mammalian BAs cross-talk with gut microbiome and shape microbial composition in a dynamic and interactive way. Read More

    The integration of chloroplast protein targeting with plant developmental and stress responses.
    BMC Biol 2017 Dec 7;15(1):118. Epub 2017 Dec 7.
    Department of Plant Biology, Michigan State University, 612 Wilson Road, Room 166, East Lansing, MI, 48824-1312, USA.
    The plastids, including chloroplasts, are a group of interrelated organelles that confer photoautotrophic growth and the unique metabolic capabilities that are characteristic of plant systems. Plastid biogenesis relies on the expression, import, and assembly of thousands of nuclear encoded preproteins. Plastid proteomes undergo rapid remodeling in response to developmental and environmental signals to generate functionally distinct plastid types in specific cells and tissues. Read More

    A multi-trait systems approach reveals a response cascade to bleaching in corals.
    BMC Biol 2017 Dec 7;15(1):117. Epub 2017 Dec 7.
    School of Life Sciences, University of Technology Sydney, Ultimo, 2007, NSW, Australia.
    Background: Climate change causes the breakdown of the symbiotic relationships between reef-building corals and their photosynthetic symbionts (genus Symbiodinium), with thermal anomalies in 2015-2016 triggering the most widespread mass coral bleaching on record and unprecedented mortality on the Great Barrier Reef. Targeted studies using specific coral stress indicators have highlighted the complexity of the physiological processes occurring during thermal stress, but have been unable to provide a clear mechanistic understanding of coral bleaching.

    Results: Here, we present an extensive multi-trait-based study in which we compare the thermal stress responses of two phylogenetically distinct and widely distributed coral species, Acropora millepora and Stylophora pistillata, integrating 14 individual stress indicators over time across a simulated thermal anomaly. Read More

    Telomere heterogeneity linked to metabolism and pluripotency state revealed by simultaneous analysis of telomere length and RNA-seq in the same human embryonic stem cell.
    BMC Biol 2017 Dec 8;15(1):114. Epub 2017 Dec 8.
    State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, 300071, China.
    Background: Telomere length heterogeneity has been detected in various cell types, including stem cells and cancer cells. Cell heterogeneity in pluripotent stem cells, such as embryonic stem cells (ESCs), is of particular interest; however, the implication and mechanisms underlying the heterogeneity remain to be understood. Single-cell analysis technology has recently been developed and effectively employed to investigate cell heterogeneity. Read More

    Dorsal spine evolution in threespine sticklebacks via a splicing change in MSX2A.
    BMC Biol 2017 Dec 7;15(1):115. Epub 2017 Dec 7.
    Department of Developmental Biology, Stanford University School of Medicine, Stanford, CA, USA.
    Background: Dorsal spine reduction in threespine sticklebacks (Gasterosteus aculeatus) is a classic example of recurrent skeletal evolution in nature. Sticklebacks in marine environments typically have long spines that form part of their skeletal armor. Many derived freshwater populations have evolved shorter spines. Read More

    On causal roles and selected effects: our genome is mostly junk.
    BMC Biol 2017 Dec 5;15(1):116. Epub 2017 Dec 5.
    Department of Biochemistry and Molecular Biology, Dalhousie University, Halifax, Nova Scotia, Canada.
    The idea that much of our genome is irrelevant to fitness-is not the product of positive natural selection at the organismal level-remains viable. Claims to the contrary, and specifically that the notion of "junk DNA" should be abandoned, are based on conflating meanings of the word "function". Recent estimates suggest that perhaps 90% of our DNA, though biochemically active, does not contribute to fitness in any sequence-dependent way, and possibly in no way at all. Read More

    PPARα is essential for retinal lipid metabolism and neuronal survival.
    BMC Biol 2017 Nov 28;15(1):113. Epub 2017 Nov 28.
    Department of Physiology, University of Oklahoma Health Sciences Center, 941 Stanton L. Young Blvd., BSEB 328B, Oklahoma City, OK, 73104, USA.
    Background: Peroxisome proliferator activated receptor-alpha (PPARα) is a ubiquitously expressed nuclear receptor. The role of endogenous PPARα in retinal neuronal homeostasis is unknown. Retinal photoreceptors are the highest energy-consuming cells in the body, requiring abundant energy substrates. Read More

    Smad4 SUMOylation is essential for memory formation through upregulation of the skeletal myopathy gene TPM2.
    BMC Biol 2017 Nov 28;15(1):112. Epub 2017 Nov 28.
    Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan.
    Background: Smad4 is a critical effector of TGF-β signaling that regulates a variety of cellular functions. However, its role in the brain has rarely been studied. Here, we examined the molecular mechanisms underlying the post-translational regulation of Smad4 function by SUMOylation, and its role in spatial memory formation. Read More

    Whole transcriptome RNA-Seq analysis reveals extensive cell type-specific compartmentalization in Volvox carteri.
    BMC Biol 2017 Nov 28;15(1):111. Epub 2017 Nov 28.
    Department of Cellular and Developmental Biology of Plants, University of Bielefeld, Universitätsstr. 25, 33615, Bielefeld, Germany.
    Background: One of evolution's most important achievements is the development and radiation of multicellular organisms with different types of cells. Complex multicellularity has evolved several times in eukaryotes; yet, in most lineages, an investigation of its molecular background is considerably challenging since the transition occurred too far in the past and, in addition, these lineages evolved a large number of cell types. However, for volvocine green algae, such as Volvox carteri, multicellularity is a relatively recent innovation. Read More

    Hybrid de novo genome assembly and centromere characterization of the gray mouse lemur (Microcebus murinus).
    BMC Biol 2017 Nov 16;15(1):110. Epub 2017 Nov 16.
    Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, 77030, USA.
    Background: The de novo assembly of repeat-rich mammalian genomes using only high-throughput short read sequencing data typically results in highly fragmented genome assemblies that limit downstream applications. Here, we present an iterative approach to hybrid de novo genome assembly that incorporates datasets stemming from multiple genomic technologies and methods. We used this approach to improve the gray mouse lemur (Microcebus murinus) genome from early draft status to a near chromosome-scale assembly. Read More

    Targeting protein quality control pathways in breast cancer.
    BMC Biol 2017 Nov 16;15(1):109. Epub 2017 Nov 16.
    Department of Biological Sciences, University of Pittsburgh, A320 Langley Hall, 4249 Fifth Ave, Pittsburgh, PA, 15260, USA.
    The efficient production, folding, and secretion of proteins is critical for cancer cell survival. However, cancer cells thrive under stress conditions that damage proteins, so many cancer cells overexpress molecular chaperones that facilitate protein folding and target misfolded proteins for degradation via the ubiquitin-proteasome or autophagy pathway. Stress response pathway induction is also important for cancer cell survival. Read More

    A yeast two-hybrid system for the screening and characterization of small-molecule inhibitors of protein-protein interactions identifies a novel putative Mdm2-binding site in p53.
    BMC Biol 2017 Nov 9;15(1):108. Epub 2017 Nov 9.
    Bioinformatics Institute, 30 Biopolis Street, #07-01, Matrix, Singapore, 138671, Singapore.
    Background: Protein-protein interactions (PPIs) are fundamental to the growth and survival of cells and serve as excellent targets to develop inhibitors of biological processes such as host-pathogen interactions and cancer cell proliferation. However, isolation of PPI inhibitors is extremely challenging. While several in vitro assays to screen for PPI inhibitors are available, they are often expensive, cumbersome, and require large amounts of purified protein. Read More

    Divide and conquer? Size adjustment with allometry and intermediate outcomes.
    BMC Biol 2017 Nov 9;15(1):107. Epub 2017 Nov 9.
    Evolution & Ecology Research Centre and School of Biological, Earth and Environmental Sciences, University of New South Wales, Sydney, NSW, 2052, Australia.
    Many trait measurements are size-dependent, and while we often divide these traits by size before fitting statistical models to control for the effect of size, this approach does not account for allometry and the intermediate outcome problem. We describe these problems and outline potential solutions. Read More

    RNA-binding activity of TRIM25 is mediated by its PRY/SPRY domain and is required for ubiquitination.
    BMC Biol 2017 Nov 8;15(1):105. Epub 2017 Nov 8.
    Wellcome Centre for Cell Biology, University of Edinburgh, Michael Swann Building, Edinburgh, EH9 3BF, UK.
    Background: TRIM25 is a novel RNA-binding protein and a member of the Tripartite Motif (TRIM) family of E3 ubiquitin ligases, which plays a pivotal role in the innate immune response. However, there is scarce knowledge about its RNA-related roles in cell biology. Furthermore, its RNA-binding domain has not been characterized. Read More

    Erv1 of Arabidopsis thaliana can directly oxidize mitochondrial intermembrane space proteins in the absence of redox-active Mia40.
    BMC Biol 2017 Nov 8;15(1):106. Epub 2017 Nov 8.
    Cell Biology, University of Kaiserslautern, Erwin-Schrödinger-Strasse 13, 67663, Kaiserslautern, Germany.
    Background: Many proteins of the mitochondrial intermembrane space (IMS) contain structural disulfide bonds formed by the mitochondrial disulfide relay. In fungi and animals, the sulfhydryl oxidase Erv1 'generates' disulfide bonds that are passed on to the oxidoreductase Mia40, which oxidizes substrate proteins. A different structural organization of plant Erv1 proteins compared to that of animal and fungal orthologs was proposed to explain its inability to complement the corresponding yeast mutant. Read More

    Characterization of a thalamic nucleus mediating habenula responses to changes in ambient illumination.
    BMC Biol 2017 Oct 31;15(1):104. Epub 2017 Oct 31.
    Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, 636921, Singapore.
    Background: Neural activity in the vertebrate habenula is affected by ambient illumination. The nucleus that links photoreceptor activity with the habenula is not well characterized. Here, we describe the location, inputs and potential function of this nucleus in larval zebrafish. Read More

    Optical inhibition of larval zebrafish behaviour with anion channelrhodopsins.
    BMC Biol 2017 Nov 3;15(1):103. Epub 2017 Nov 3.
    Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore.
    Background: Optical silencing of activity provides a way to test the necessity of neurons in behaviour. Two light-gated anion channels, GtACR1 and GtACR2, have recently been shown to potently inhibit activity in cultured mammalian neurons and in Drosophila. Here, we test the usefulness of these channels in larval zebrafish, using spontaneous coiling behaviour as the assay. Read More

    Membrane dynamics and organelle biogenesis-lipid pipelines and vesicular carriers.
    BMC Biol 2017 Oct 31;15(1):102. Epub 2017 Oct 31.
    Montreal Neurological Institute, McGill University, 3801 University Avenue, Montreal, Quebec, H3A 2B4, Canada.
    Discoveries spanning several decades have pointed to vital membrane lipid trafficking pathways involving both vesicular and non-vesicular carriers. But the relative contributions for distinct membrane delivery pathways in cell growth and organelle biogenesis continue to be a puzzle. This is because lipids flow from many sources and across many paths via transport vesicles, non-vesicular transfer proteins, and dynamic interactions between organelles at membrane contact sites. Read More

    MultiBac: from protein complex structures to synthetic viral nanosystems.
    BMC Biol 2017 Oct 30;15(1):99. Epub 2017 Oct 30.
    The School of Biochemistry and Bristol Synthetic Biology Centre BrisSynBio, University of Bristol, Tankard's Close, Bristol, BS8 1TD, UK.
    The MultiBac baculovirus/insect cell expression vector system was conceived as a user-friendly, modular tool-kit for producing multiprotein complexes for structural biology applications. MultiBac has allowed the structure and function of many molecular machines to be elucidated, including previously inaccessible high-value drug targets. More recently, MultiBac developments have shifted to customized baculoviral genomes that are tailored for a range of applications, including synthesizing artificial proteins by genetic code expansion. Read More

    Digital tissue and what it may reveal about the brain.
    BMC Biol 2017 Oct 30;15(1):101. Epub 2017 Oct 30.
    Department of Molecular and Cellular Biology, Center for Brain Science, Harvard University, Cambridge, MA, 02138, USA.
    Imaging as a means of scientific data storage has evolved rapidly over the past century from hand drawings, to photography, to digital images. Only recently can sufficiently large datasets be acquired, stored, and processed such that tissue digitization can actually reveal more than direct observation of tissue. One field where this transformation is occurring is connectomics: the mapping of neural connections in large volumes of digitized brain tissue. Read More

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