bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reticulon and CLIMP-63 control nanodomain organization of peripheral ER tubules
Authors: Gao Guang , Zhu Chengjia , Liu Emma , Nabi Ivan R. 
Published: February 2019

AbstractThe endoplasmic reticulum (ER) is an expansive, membrane-enclosed organelle composed of smooth peripheral tubules and rough, ribosome-studded central ER sheets whose morphology is determined, in part, by the ER-shaping proteins, reticulon and CLIMP-63, respectively. Here, STimulated Emission Depletion (STED) super-resolution microscopy shows that reticulon and CLIMP-63 also control the organization and dynamics of peripheral ER tubule nanodomains. STED imaging shows that lumenal ERmoxGFP, membrane Sec61βGFP, knock-in calreticulin-GFP and antibody-labeled ER resident proteins calnexin and derlin-1 are all localized to periodic puncta along the length of peripheral ER tubules that are not readily observable by diffraction limited confocal microscopy. Reticulon segregates away from and restricts lumenal blob length while CLIMP-63 associates with and increases lumenal blob length. Reticulon and CLIMP-63 also regulate the nanodomain distribution of ER resident proteins, being required for the preferential segregation of calnexin and derlin-1 puncta away from lumenal ERmoxGFP blobs. High-speed (40 ms/frame) live cell STED imaging shows that reticulon and CLIMP-63 control nanoscale compartmentalization of lumenal flow in peripheral ER tubules. Reticulon enhances and CLIMP-63 disrupts the local accumulation of lumenal ERmoxGFP at spatially defined sites along ER tubules. The ER shaping proteins reticulon and CLIMP-63 therefore control lumenal ER nanodomain dynamics, heterogeneity and interaction with ER resident proteins in peripheral ER tubules.
Sets of Co-regulated Serum Lipids are Associated with Alzheimer Disease Pathophysiology
Authors: Barupal Dinesh Kumar , Bailli Rebecca , Fan Sili , Saykin Andrew J. , Meikle Peter J. , Arnold Matthias , Nho Kwangsik , Fiehn Oliver , Kaddurah-Daouk Rima ,   for the Alzheimer’s Disease Neuroimaging Initiative,   the Alzheimer Disease Metabolomics Consortium
Published: February 2019

ABSTRACTINTRODUCTIONAltered regulation of lipid metabolism in Alzheimer disease (AD) can be characterized using lipidomic profiling.METHOD349 serum lipids were measured in 806 participants enrolled in the Alzheimer Disease Neuroimaging Initiative Phase 1 (ADNI1) cohort and analysed using lipid regression models and lipid set enrichment statistics.RESULTSAD diagnosis was associated with 7 of 28 lipid sets of which four also correlated with cognitive decline, including polyunsaturated fatty acids. CSF amyloid beta Aβ1-42 correlated with glucosylceramides, lysophosphatidyl cholines and unsaturated triacylglycerides; CSF total tau and brain atrophy correlated with monounsaturated sphingomyelins and ceramides, in addition to EPA-containing lipids.DISCUSSIONLipid desaturation, elongation and acyl chain remodeling are dysregulated across the spectrum of AD pathogenesis. Monounsaturated lipids were important in early stages of AD, while polyunsaturated lipid metabolism was associated with later stages of AD.SIGNFICANCEBoth metabolic genes and co-morbidity with metabolic diseases indicate that lipid metabolism is critical in the etiology of Alzheimer’s disease (AD). For 800 subjects, we found that sets of blood lipids were associated with current AD-biomarkers and with AD clinical symptoms. Our study highlights the role of disturbed acyl chain lipid remodelling in several lipid classes. Our work has significant implications on finding a cure for AD. Depending on subject age, human blood lipids may have different effects on AD development. Remodelling of acyl chains needs to be studied in relation to genetic variants and environmental factors. Specifically, the impact of dietary supplements and drugs on lipid remodelling must be investigated.
Rare Microbial Taxa Emerge When Communities Collide: Freshwater and Marine Microbiome Responses to Experimental Seawater Intrusion
Authors: Rocca Jennifer D. , Simonin Marie , Wright Justin P. , Washburne Alex , Bernhardt Emily 
Published: February 2019

AbstractWhole microbial communities regularly merge with one another, often in tandem with their environments, in a process called community coalescence. Such events allow us to address a central question in ecology – what processes shape community assembly. We used a reciprocal transplant and mixing experiment to directly and independently unravel the effects of environmental filtering and biotic interactions on microbiome success when freshwater and marine communities coalesce. The brackish treatment and community mixing resulted in strong convergence of microbiome structure and function toward the marine. Brackish exposure imposed a 96% taxa loss from freshwater and 66% loss from marine microbiomes, which was somewhat counterbalanced by the emergence of tolerant rare taxa. Community mixing further resulted in 29% and 49% loss from biotic interactions between freshwater and marine microbiomes, offset somewhat by mutualistically-assisted rare microbial taxa. Our study emphasizes the importance of the rare biosphere as a critical component of community resilience.
An integrative approach identifies direct targets of the late viral transcription complex and an expanded promoter recognition motif in Kaposi’s sarcoma-associated herpesvirus
Authors: Nandakumar Divya , Glaunsinger Britt 
Published: February 2019

AbstractThe structural proteins of DNA viruses are generally encoded by late genes, whose expression relies on recruitment of the host transcriptional machinery only after the onset of viral genome replication. β and γ-herpesviruses encode a unique six-member viral pre-initiation complex (vPIC) for this purpose, although how the vPIC directs specific activation of late genes remains largely unknown. The specificity underlying late transcription is particularly notable given that late gene promoters are unusually small, with a modified TATA-box being the only recognizable element. Here, we explored the basis for this specificity using an integrative approach to evaluate vPIC-dependent gene expression combined with promoter occupancy during Kaposi’s sarcoma-associated herpesvirus (KSHV) infection. This approach distinguished the direct and indirect targets of the vPIC, ultimately revealing a novel promoter motif critical for KSHV vPIC binding. Additionally, we found that the KSHV vPIC component ORF24 is required for efficient viral DNA replication. Together, these results identify an elusive element that contributes to vPIC specificity and suggest novel links between KSHV DNA replication and late transcription.Author summaryGene expression in DNA viruses often occurs in temporal waves, with expression of essential structural proteins occurring late in infection, after viral genome replication has begun. Strategies underlying expression of these viral late genes are often sophisticated; for example, the β- and γ-herpesviruses encode a six-component viral complex that directs late gene transcription, largely by unknown mechanisms. Here, we evaluated how this complex specifically recognizes late promoters during infection with the oncogenic human γ-herpesvirus Kaposi’s sarcoma-associated herpesvirus (KSHV). We found that one of the components of the late transcription complex was required for robust viral DNA replication, suggesting new links between KSHV replication and transcription. Combined measurements of late gene expression and promoter occupancy then revealed which KHSV genes are directly controlled by the late gene transcription complex, leading to identification of a key new regulatory element in KSHV late promoters. Together, these data help explain how the late gene transcription complex is able to bind seemingly minimal promoters with high specificity, ensuring robust expression of viral factors necessary for assembly of progeny virions.
Tracking activity patterns of a multispecies community of gymnotiform weakly electric fish in their neotropical habitat without tagging
Authors: Henninger Jörg , Krahe Rüdiger , Sinz Fabian , Benda Jan 
Published: February 2019

AbstractField studies on freely behaving animals commonly require tagging and often are focused on single species. Weakly electric fish generate a species- and individual-specific electric organ discharge (EOD) and therefore provide a unique opportunity for individual tracking without tagging. We here present and test tracking algorithms based on recordings with submerged electrode arrays. Harmonic structures extracted from power spectra provide fish identity. Localization of fish based on weighted averages of their EOD amplitudes is found to be more robust than fitting a dipole model. We apply these techniques to monitor a community of three species,Apteronotus rostratus,Eigenmannia humboldtii, andSternopygus dariensis, in their natural habitat in Darién, Panamá. We found consistent upstream movements after sunset followed by downstream movements in the second half of the night. Extrapolations of these movements and estimates of fish density obtained from additional transect data suggest that some fish cover at least several hundreds of meters of the stream per night. Most fish, includingEigenmannia, were traversing the electrode array solitarily. Fromin-situmeasurements of the decay of the EOD amplitude with distance of individual animals we estimated that fish can detect conspecifics at distances of up to 2 m. Our recordings also emphasize the complexity of natural electrosensory scenes resulting from the interactions of the EODs of different species. Electrode arrays thus provide an unprecedented window into the so-far hidden nocturnal activities of multispecies communities of weakly electric fish at an unmatched level of detail.Summary statementDetailed movement patterns and complex electrosensory scenes of three species of weakly electric fish were tracked without tagging using a submerged electrode array in a small Neotropical stream.
Extracellular Pgk1 enhances neurite outgrowth of motoneurons through Nogo66-independent targeting of NogoA
Authors: Lin Cheng Yung , Wu Chia Lun , Lee Kok Zhi , Chen You Jei , Zhang Po Hsiang , Chang Chia Yu , Han Horng Jyh , Lin Shinn Zong , Tsai Huai Jen 
Published: February 2019

AbstractNogoA inhibits neurite outgrowth of motoneurons (NOM) through interaction with its receptors, Nogo66/NgR. Inhibition of Nogo receptors rescues NOM, but not to the extent exhibited by NogoA-knockout mice, suggesting the presence of other pathways. We found that NogoA-overexpressing muscle cells reduced phosphoglycerate kinase 1 (Pgk1) secretion, resulting in inhibiting NOM. Apart from its glycolytic role and independent of the Nogo66 pathway, extracellular Pgk1 stimulated NOM by triggering a reduction of p-Cofilin-S3, a growth cone collapse marker, through decreasing a novel Rac1-GTP/p-Pak1-T423/p-P38-T180/p-MK2-T334/p-Limk1-S323/p-Cofilin-S3 molecular pathway. Not only did supplementary Pgk1 enhance NOM in defective cells, but injection of Pgk1 rescued denervation in muscle-specific NogoA-overexpression of zebrafish and an Amyotrophic Lateral Sclerosis mouse model, SOD1-G93A. Thus, Pgk1 secreted from muscle is detrimental to motoneuron synapse growth and maintenance.
Testing pleiotropy vs. separate QTL in multiparental populations
Authors: Boehm Frederick J. , Chesler Elissa J. , Yandell Brian S. , Broman Karl W. 
Published: February 2019

ABSTRACTThe high mapping resolution of multiparental populations, combined with technology to measure tens of thousands of phenotypes, presents a need for quantitative methods to enhance understanding of the genetic architecture of complex traits. When multiple traits map to a common genomic region, knowledge of the number of distinct loci provides important insight into the underlying mechanism and can assist planning for subsequent experiments. We extend the method of Jiang and Zeng (1995), for testing pleiotropy with a pair of traits, to the case of more than two alleles. We also incorporate polygenic random effects to account for population structure. We use a parametric bootstrap to determine statistical significance. We apply our methods to a behavioral genetics data set from Diversity Outbred mice, where we find evidence for presence of two distinct loci in a 2.5 cM region. Our methods have been incorporated into the R packageqtl2pleio.
BDNF controls bidirectional endocannabinoid-plasticity at corticostriatal synapses
Authors: Gangarossa Giuseppe , Perez Sylvie , Dembitskaya Yulia , Prokin Ilya , Berry Hugues , Venance Laurent 
Published: February 2019

ABSTRACTThe dorsal striatum exhibits bidirectional corticostriatal synaptic plasticity, NMDAR- and endocannabinoids-(eCB)-mediated, necessary for the encoding of procedural learning. Therefore, characterizing factors controlling corticostriatal plasticity is of crucial importance. Brain-derived neurotrophic factor (BDNF) and its receptor, the tropomyosine receptor kinase-B (TrkB), shape striatal functions and their dysfunction deeply affect basal ganglia. BDNF/TrkB signaling controls NMDAR-plasticity in various brain structures including striatum. However, despite cross-talks between BDNF and eCBs, the role of BDNF in eCB-plasticity remains unknown. Here, we show that BDNF/TrkB signaling promotes eCB-plasticity (LTD and LTP) induced by rate-based (low-frequency stimulation) or spike-timing-based (spike-timing-dependent plasticity, STDP) paradigm in striatum. We show that TrkB activation is required for the expression and the scaling of both eCB-LTD and eCB-LTP. Using two-photon imaging of the dendritic spines combined with patch-clamp recordings, we show that TrkB activation induces an intracellular calcium boost, thus increasing eCB synthesis and release. We provide a mathematical model for the dynamics of the signaling pathways involved in corticostriatal plasticity. Finally, we show that TrkB activation allows an enlargement of the domain of expression of eCB-STDP. Our results reveal a novel role for BDNF/TrkB signaling in governing eCB-plasticity expression in striatum, and thus the engram of procedural learning.
Electron cryo-microscopy structures of remodeler-nucleosome intermediates suggest allosteric control through the nucleosome
Authors: Armache Jean-Paul , Gamarra Nathan , Johnson Stephanie L. , Leonard John D. , Wu Shenping , Narlikar Geeta J. , Cheng Yifan 
Published: February 2019

AbstractThe SNF2h remodeler slides nucleosomes most efficiently as a dimer, yet how the two protomers avoid a tug-of-war is unclear. Furthermore, SNF2h couples histone octamer deformation to nucleosome sliding, but the underlying structural basis remains unknown. Here we present cryo-EM structures of SNF2h-nucleosome complexes with ADP-BeFx that capture two reaction intermediates. In one structure, histone residues near the dyad and in the H2A-H2B acidic patch, distal to the active SNF2h protomer, are disordered. The disordered acidic patch is expected to inhibit the second SNF2h promoter, while disorder near the dyad is expected to promote DNA translocation. The other structure doesn’t show octamer deformation, but surprisingly shows a 2bp translocation. FRET studies indicate that ADP-BeFx predisposes SNF2h-nucleosome complexes for an elemental translocation step. We propose a model for allosteric control through the nucleosome, where one SNF2h protomer promotes asymmetric octamer deformation to inhibit the second protomer, while stimulating directional DNA translocation.One sentence summaryCryo-EM structures capture different conformational states of chromatin remodeler-nucleosome complexes.
Flower-like patterns in multi-species biofilms
Authors: Xiong Liyang , Cao Yuansheng , Cooper Robert , Rappel Wouter-Jan , Hasty Jeff , Tsimring Lev 
Published: February 2019

AbstractDiverse interactions among species within bacterial biofilms often lead to intricate spatiotemporal dynamics. The spatial structure of biofilms can determine growth and survival of different species, but the mechanisms driving formation of this structure are not fully understood. Here, we describe the emergence of complex structures in a biofilm grown from mixtures of motile and non-motile bacterial species on a soft agar surface. Time-lapse imaging shows that non-motile bacteria “hitchhike” on the motile bacteria as the latter migrate outward. The non-motile bacteria accumulate at the boundary of the colony and trigger an instability that leaves behind striking flower-like patterns. The mechanism of the front instability governing this pattern formation is elucidated by a mathematical model for the frictional motion of the colony interface, with friction depending on the local concentration of the nonmotile species along the interface. A more elaborate two-dimensional phase-field model that explicitly accounts for the interplay between growth, mechanical stress from the motile species, and friction provided by the non-motile species, fully reproduces the observed flower-like patterns.
Mutations in the Insulator Protein Suppressor of Hairy Wing Induce Genome Instability
Authors: Hsu Shih-Jui , Stow Emily C. , Simmons James R. , Wallace Heather A. , Lopez Andrea Mancheno , Stroud Shannon , Labrador Mariano 
Published: February 2019

AbstractChromatin insulator proteins mediate the formation of contacts between distant insulator sites along chromatin fibers. Long-range contacts facilitate communication between regulatory sequences and gene promoters throughout the genome, allowing accurate gene transcription regulation during embryo development and cell differentiation. Lack of insulator function has detrimental effects often resulting in lethality. TheDrosophilainsulator protein Suppressor of Hairy wing [Su(Hw)] is not essential for viability, but plays a crucial role in female oogenesis. The mechanism(s) by which Su(Hw) promotes proper oogenesis remains unclear. To gain insight into the functional properties of chromatin insulators, we further characterize the oogenesis phenotypes ofsu(Hw)mutant females. We find that mutant egg chambers frequently display an irregular number of nurse cells, have poorly formed microtubule organization centers (MTOC) in the germarium, and show mislocalized Gurken (Grk) in later stages of oogenesis. Furthermore, eggshells produced by partially rescuedsu(Hw)mutant females exhibit dorsoventral patterning defects that are identical to defects found in spindle mutants or in piRNA pathway mutants. Further analysis reveals an excess of DNA damage in egg chambers, which is independent of activation of transposable elements, and that Gurken localization defects and oogenesis progression are partially rescued by mutations inmei-41andchk1genes. In addition, we show that Su(Hw) is required for chromosome integrity in dividing neuroblasts from larval brains. Together, these findings suggest that Su(Hw) plays a critical role in maintaining genome integrity during germline development inDrosophilafemales as well as in dividing somatic cells.
Transcriptional dynamics of bread wheat in response to nitrate and phosphate supply reveal functional divergence of genetic factors involved in nitrate and phosphate signaling
Authors: Dissanayake Indeewari , Rodriguez-Medina Joel , Brady Siobhan M. , Tanurdžić Miloš 
Published: February 2019

AbstractNitrate (N) and phosphate (P) levels are sensed by plant cells and signaled via local and systemic signaling pathways to modulate plant growth and development. Understanding the genetic basis of these signaling mechanisms is key to future improvement of nutrient use efficiency. While major progress has been made in understanding N and P signaling pathways and their interaction in the model plant Arabidopsis, understanding of transcriptional responses to N and P in a major monocot crop wheat is lacking. Therefore, we investigated gene expression dynamics of wheat roots in response to N and/or P provision using RNA-Seq. We found that nitrate presence is the major trigger for most of the transcriptional response to occur within 24 h, however, we also identified a large array of synergistic transcriptional responses to concomitant supply of N and P. Through gene co-expression analysis, we identified gene co-expression modules prominent in nitrate signaling and metabolism in wheat. Importantly, we identified likely instances of functional divergence in major N-responsive transcription factors familiesHRS1/HHOandTGAof wheat from their rice/Arabidopsis homologues. Our work broadens the understanding of wheat N and P transcriptional responses and aids in prioritizing gene candidates for production of wheat varieties that are efficient in nitrogen usage.
Autonomously replicating linear plasmids facilitate the analysis of replication origin function inCandida albicans
Authors: Bijlani Swati , Thevandavakkam Mathuravani A. , Tsai Hung-Ji , Berman Judith 
Published: February 2019

AbstractThe ability to generate autonomously replicating plasmids has been elusive inCandida albicans, a prevalent human fungal commensal and pathogen. Instead, plasmids generally integrate into the genome. Here, we assessed plasmid and transformant properties, including plasmid geometry, transformant colony size, four selectable markers, and potential origins of replication for their ability to drive autonomous plasmid maintenance. Importantly, linear plasmids with terminal telomere repeats yielded many more autonomous transformants than circular plasmids with the identical sequences.Furthermore, we could distinguish by colony size, transient, autonomously replicating and chromosomally integrated transformants (tiny, medium and large, respectively).Candida albicans URA3and a heterologous marker,ARG4,yielded many transient transformants indicative of weak origin activity; replication of plasmid carrying heterologousLEU2marker was highly dependent upon the addition of abona fideorigin sequence. Severalbona fidechromosomal origins, with an origin fragment of ~100 bp as well as a heterologous origin,panARS, fromKluyveromyces lactisdrove autonomous replication, yielding moderate transformation efficiency and plasmid stability. Thus,C. albicansmaintains linear plasmids that yield high transformation efficiency and are maintained autonomously in an origin-dependent manner.ImportanceCircular plasmids are important tools for molecular manipulation in model fungi such as baker’s yeast, yet, inCandida albicans, an important yeast pathogen of humans, prior studies were not able to generate circular plasmids that were autonomous (duplicated without inserting themselves into the chromosome). Here, we found that linearizing circular plasmids with sequences from telomeres, the chromosome ends, allows the plasmids to duplicate and segregate inC. albicans.We used this system to identify chromosomal sequences that facilitate the initiation of plasmid replication (origins) and to show that a ~100 bp fragment of aC. albicansorigin, as well as an origin sequence from a distantly related yeast, can both function as origins inC. albicans.Thus, the requirements for plasmid geometry, but not necessarily for origin sequences, differ betweenC. albicansand baker’s yeast.