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BMC Biology

Mei Zhu, Giuseppe P Cortese, Clarissa L Waites
BACKGROUND: Parkinson's disease (PD)-associated E3 ubiquitin ligase Parkin is enriched at glutamatergic synapses, where it ubiquitinates multiple substrates, suggesting that its mutation/loss-of-function could contribute to the etiology of PD by disrupting excitatory neurotransmission. Here, we evaluate the impact of four common PD-associated Parkin point mutations (T240M, R275W, R334C, G430D) on glutamatergic synaptic function in hippocampal neurons. RESULTS: We find that expression of these point mutants in cultured hippocampal neurons from Parkin-deficient and Parkin-null backgrounds alters NMDA and AMPA receptor-mediated currents and cell-surface levels and prevents the induction of long-term depression...
September 10, 2018: BMC Biology
Stephen J Smith
Array tomography encompasses light and electron microscopy modalities that offer unparalleled opportunities to explore three-dimensional cellular architectures in extremely fine structural and molecular detail. Fluorescence array tomography achieves much higher resolution and molecular multiplexing than most other fluorescence microscopy methods, while electron array tomography can capture three-dimensional ultrastructure much more easily and rapidly than traditional serial-section electron microscopy methods...
September 6, 2018: BMC Biology
Pauline Salis, Natacha Roux, Olivier Soulat, David Lecchini, Vincent Laudet, Bruno Frédérich
BACKGROUND: Biologists have long been fascinated by the striking diversity of complex color patterns in tropical reef fishes. However, the origins and evolution of this diversity are still poorly understood. Disentangling the evolution of simple color patterns offers the opportunity to dissect both ultimate and proximate causes underlying color diversity. RESULTS: Here, we study clownfishes, a tribe of 30 species within the Pomacentridae that displays a relatively simple color pattern made of zero to three vertical white stripes on a dark body background...
September 5, 2018: BMC Biology
Daniella Lucena, Marco Mauri, Felix Schmidt, Bruno Eckhardt, Peter L Graumann
BACKGROUND: Proteins within the cytoplasmic membrane display distinct localization patterns and arrangements. While multiple models exist describing the dynamics of membrane proteins, to date, there have been few systematic studies, particularly in bacteria, to evaluate how protein size, number of transmembrane domains, and temperature affect their diffusion, and if conserved localization patterns exist. RESULTS: We have used fluorescence microscopy, single-molecule tracking (SMT), and computer-aided visualization methods to obtain a better understanding of the three-dimensional organization of bacterial membrane proteins, using the model bacterium Bacillus subtilis...
September 3, 2018: BMC Biology
Steven L Salzberg
Seventeen years after the initial publicationx of the human genome, we still haven't found all of our genes. The answer turns out to be more complex than anyone had imagined when the Human Genome Project began.
August 20, 2018: BMC Biology
Thomas Flatt, Linda Partridge
Between the 1930s and 50s, evolutionary biologists developed a successful theory of why organisms age, firmly rooted in population genetic principles. By the 1980s the evolution of aging had a secure experimental basis. Since the force of selection declines with age, aging evolves due to mutation accumulation or a benefit to fitness early in life. Here we review major insights and challenges that have emerged over the last 35 years: selection does not always necessarily decline with age; higher extrinsic (i...
August 20, 2018: BMC Biology
Tomer Shlamkovich, Lidan Aharon, Dana Koslawsky, Yulia Einav, Niv Papo
BACKGROUND: Increased activity of the receptor tyrosine kinase Tie2 has been implicated in the promotion of pathological angiogenesis. This activity is mainly mediated through angiopoietin (Ang)1- and Ang2-dependent activation of integrins by Tie2, rendering the Ang/Tie2/integrin axis an attractive putative target for cancer therapeutics. RESULTS: To target this axis, we developed single domain, non-immunoglobulin high-affinity bi-specific protein inhibitors against both Tie2 and αv β3 integrin...
August 17, 2018: BMC Biology
Alberto Santos-Zavaleta, Mishael Sánchez-Pérez, Heladia Salgado, David A Velázquez-Ramírez, Socorro Gama-Castro, Víctor H Tierrafría, Stephen J W Busby, Patricia Aquino, Xin Fang, Bernhard O Palsson, James E Galagan, Julio Collado-Vides
BACKGROUND: Our understanding of the regulation of gene expression has benefited from the availability of high-throughput technologies that interrogate the whole genome for the binding of specific transcription factors and gene expression profiles. In the case of widely used model organisms, such as Escherichia coli K-12, the new knowledge gained from these approaches needs to be integrated with the legacy of accumulated knowledge from genetic and molecular biology experiments conducted in the pre-genomic era in order to attain the deepest level of understanding possible based on the available data...
August 16, 2018: BMC Biology
Romain Libbrecht, Peter R Oxley, Daniel J C Kronauer
BACKGROUND: Division of labor between reproductive queens and workers that perform brood care is a hallmark of insect societies. However, studies of the molecular basis of this fundamental dichotomy are limited by the fact that the caste of an individual cannot typically be experimentally manipulated at the adult stage. Here we take advantage of the unique biology of the clonal raider ant, Ooceraea biroi, to study brain gene expression dynamics during experimentally induced transitions between reproductive and brood care behavior...
August 13, 2018: BMC Biology
Joanna Koszela, Nhan T Pham, David Evans, Stefan Mann, Irene Perez-Pi, Steven Shave, Derek F J Ceccarelli, Frank Sicheri, Mike Tyers, Manfred Auer
BACKGROUND: The ubiquitin-proteasome system (UPS) controls the stability, localization and/or activity of the proteome. However, the identification and characterization of complex individual ubiquitination cascades and their modulators remains a challenge. Here, we report a broadly applicable, multiplexed, miniaturized on-bead technique for real-time monitoring of various ubiquitination-related enzymatic activities. The assay, termed UPS-confocal fluorescence nanoscanning (UPS-CONA), employs a substrate of interest immobilized on a micro-bead and a fluorescently labeled ubiquitin which, upon enzymatic conjugation to the substrate, is quantitatively detected on the bead periphery by confocal imaging...
August 10, 2018: BMC Biology
Jan Krefting, Miguel A Andrade-Navarro, Jonas Ibn-Salem
BACKGROUND: The human genome is highly organized in the three-dimensional nucleus. Chromosomes fold locally into topologically associating domains (TADs) defined by increased intra-domain chromatin contacts. TADs contribute to gene regulation by restricting chromatin interactions of regulatory sequences, such as enhancers, with their target genes. Disruption of TADs can result in altered gene expression and is associated to genetic diseases and cancers. However, it is not clear to which extent TAD regions are conserved in evolution and whether disruption of TADs by evolutionary rearrangements can alter gene expression...
August 7, 2018: BMC Biology
Moein Esghaei, Mohammad Reza Daliri, Stefan Treue
BACKGROUND: The timing of action potentials ("spikes") of cortical neurons has been shown to be aligned to the phase of low-frequency (< 10 Hz) local field potentials (LFPs) in several cortical areas. However, across the areas, this alignment varies and the role of this spike-phase coupling (SPC) in cognitive functions is not well understood. RESULTS: Here, we propose a role in the coordination of neural activity by selective attention. After refining previous analytical methods for measuring SPC, we show that first, SPC is present along the dorsal processing pathway in macaque visual cortex (area MT); second, spikes occur in falling phases of the low-frequency LFP independent of the location of spatial attention; third, switching spatial attention into the receptive field (RF) of MT neurons decreases this coupling; and finally, the LFP phase causally influences the spikes...
August 6, 2018: BMC Biology
Parameswaran Hariharan, Elena Tikhonova, João Medeiros-Silva, Aike Jeucken, Mikhail V Bogdanov, William Dowhan, Jos F Brouwers, Markus Weingarth, Lan Guan
BACKGROUND: Membrane lipids play critical roles in the structure and function of membrane-embedded transporters. Salmonella typhimurium MelB (MelBSt ) is a symporter coupling melibiose translocation with a cation (Na+ , Li+ , or H+ ). We present an extensive study on the effects of specific phospholipids on the structure of MelBSt and the melibiose transport catalyzed by this protein. RESULTS: Lipidomic analysis and thin-layer chromatography (TLC) experiments reveal that at least one phosphatidylethanolamine (PE) and one phosphatidylglycerol (PG) molecule associate with MelBSt at high affinities...
August 3, 2018: BMC Biology
Elvire Berthenet, Koji Yahara, Kaisa Thorell, Ben Pascoe, Guillaume Meric, Jane M Mikhail, Lars Engstrand, Helena Enroth, Alain Burette, Francis Megraud, Christine Varon, John C Atherton, Sinead Smith, Thomas S Wilkinson, Matthew D Hitchings, Daniel Falush, Samuel K Sheppard
BACKGROUND: Helicobacter pylori are stomach-dwelling bacteria that are present in about 50% of the global population. Infection is asymptomatic in most cases, but it has been associated with gastritis, gastric ulcers and gastric cancer. Epidemiological evidence shows that progression to cancer depends upon the host and pathogen factors, but questions remain about why cancer phenotypes develop in a minority of infected people. Here, we use comparative genomics approaches to understand how genetic variation amongst bacterial strains influences disease progression...
August 2, 2018: BMC Biology
Martin Bens, Karol Szafranski, Susanne Holtze, Arne Sahm, Marco Groth, Hans A Kestler, Thomas B Hildebrandt, Matthias Platzer
BACKGROUND: Naked mole-rats (NMRs) are eusocially organized in colonies. Although breeders carry the additional metabolic load of reproduction, they are extremely long-lived and remain fertile throughout their lifespan. This phenomenon contrasts the disposable soma theory of aging stating that organisms can invest their resources either in somatic maintenance, enabling a longer lifespan, or in reproduction, at the cost of longevity. Here, we present a comparative transcriptome analysis of breeders vs...
August 2, 2018: BMC Biology
Ivonne Heinze, Martin Bens, Enrico Calzia, Susanne Holtze, Oleksandr Dakhovnik, Arne Sahm, Joanna M Kirkpatrick, Karol Szafranski, Natalie Romanov, Sai Nagender Sama, Kerstin Holzer, Stephan Singer, Maria Ermolaeva, Matthias Platzer, Thomas Hildebrandt, Alessandro Ori
BACKGROUND: Mammals display a wide range of variation in their lifespan. Investigating the molecular networks that distinguish long- from short-lived species has proven useful to identify determinants of longevity. Here, we compared the livers of young and old long-lived naked mole-rats (NMRs) and the phylogenetically closely related, shorter-lived, guinea pigs using an integrated omics approach. RESULTS: We found that NMR livers display a unique expression pattern of mitochondrial proteins that results in distinct metabolic features of their mitochondria...
August 2, 2018: BMC Biology
Edward A Hayter, Timothy M Brown
BACKGROUND: Intrinsically photosensitive retinal ganglion cells (ipRGCs) drive an array of non-image-forming (NIF) visual responses including circadian photoentrainment and the pupil light reflex. ipRGCs integrate extrinsic (rod/cone) and intrinsic (melanopsin) photoreceptive signals, but the contribution of cones to ipRGC-dependent responses remains incompletely understood. Given recent data revealing that cone-derived colour signals influence mouse circadian timing and pupil responses in humans, here we set out to investigate the role of colour information in pupil control in mice...
July 31, 2018: BMC Biology
Geneviève Arsenault-Labrecque, Humira Sonah, Amandine Lebreton, Caroline Labbé, Geneviève Marchand, Allen Xue, François Belzile, Brian J Knaus, Niklaus J Grünwald, Richard R Bélanger
BACKGROUND: The interaction between oomycete plant pathogen Phytophthora sojae and soybean is characterized by the presence of avirulence (Avr) genes in P. sojae, which encode for effectors that trigger immune responses and resistance in soybean via corresponding resistance genes (Rps). A recent survey highlighted a rapid diversification of P. sojae Avr genes in soybean fields and the need to deploy new Rps genes. However, the full genetic diversity of P. sojae isolates remains complex and dynamic and is mostly characterized on the basis of phenotypic associations with differential soybean lines...
July 26, 2018: BMC Biology
Christian Münch
Mitochondria are sensitive to numerous environmental stresses, which can lead to activation of mitochondrial stress responses (MSRs). Of particular recent interest has been the mitochondrial unfolded protein response (UPRmt ), activated to restore protein homeostasis (proteostasis) upon mitochondrial protein misfolding. Several axes of the UPRmt have been described, creating some confusion as to the nature of the different responses. While distinct molecularly, these different axes are likely mutually beneficial and activated in parallel...
July 26, 2018: BMC Biology
Parvathy Krishnan, Lukas Meile, Clémence Plissonneau, Xin Ma, Fanny E Hartmann, Daniel Croll, Bruce A McDonald, Andrea Sánchez-Vallet
BACKGROUND: Fungal plant pathogens pose major threats to crop yield and sustainable food production if they are highly adapted to their host and the local environment. Variation in gene expression contributes to phenotypic diversity within fungal species and affects adaptation. However, very few cases of adaptive regulatory changes have been reported in fungi and the underlying mechanisms remain largely unexplored. Fungal pathogen genomes are highly plastic and harbor numerous insertions of transposable elements, which can potentially contribute to gene expression regulation...
July 16, 2018: BMC Biology
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