bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluating the stoichiometric trait distributions of cultured bacterial populations and uncultured microbial communities
Authors: Manzella Michael , Geiss Roy , Hall E.K.
Published: February 2019

Originality Statement

The ecological stoichiometry of microbial biomass has most often focused on the ratio of the biologically-important elements carbon (C), nitrogen (N), and phosphorus (P) and has primarily been examined at a resolution where the contribution of the individual is masked by the reported population or community average. However, reporting population or community averages makes it difficult to assess phenotypic plasticity and stochasticity and mask important information required to understand both the drivers and implications of microbial biomass stoichiometry in nature. One way to assess the diversity of individual microbial phenotypes is through the use of single-cell techniques such as energy dispersive spectroscopy (EDS). EDS reports cellular quotas for the majority of elements composing microbial biomass including C, N, and P. In this study, by measuring individual cells within a microbial community or population, we describe for the first time the stoichiometry of microbial biomass as a distribution instead of an average. Exploration of stoichiometric trait distributions (as presented here) has the potential to improve our understanding of how nutrients interact with individual microorganisms to structure the elemental content of bacterial biomass and better describe how bacterial community biomass affects the ecosystems within which these organisms exist.

To assess the potential for EDS to describe the stoichiometric variance within populations and communities we measured the stoichiometric trait distribution of cultured freshwater bacterial populations under different resource conditions and compared them to natural microbial communities sampled from three lakes. Mean biomass C:N:P values obtained by EDS matched closely to those obtained by bulk measures using traditional analytical techniques for each freshwater isolate. However, we observed pronounced differences in the stoichiometric trait distributions of freshwater bacterial isolates compared to the stoichiometric trait distributions of natural communities. The stoichiometric trait distribution of the environmental isolates changed with P availability, growth phase, and genotype, with P availability having the strongest effect. The distribution of biomass ratios within each isolate growth experiment were the most constrained during stages of rapid growth and commonly had unimodal distributions. In contrast to the population distributions, the distribution of N:P and C:P for a similar number of cells from each of the mixed lake communities had narrower stoichiometric distributions and more commonly exhibited multiple modes.
Reticulon and CLIMP-63 control nanodomain organization of peripheral ER tubules
Authors: Gao Guang , Zhu Chengjia , Liu Emma , Nabi Ivan R.
Published: February 2019

The 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

INTRODUCTION

Altered regulation of lipid metabolism in Alzheimer disease (AD) can be characterized using lipidomic profiling.

METHOD

349 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.

RESULTS

AD 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.

DISCUSSION

Lipid 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.

SIGNFICANCE

Both 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

Whole 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

The 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 summary

Gene 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

Field 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 statement

Detailed 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

NogoA 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

The 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

The 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

The 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 summary

Cryo-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

Diverse 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

Chromatin 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

Nitrate (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

The 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.

Importance

Circular 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.
Host_microbe_PPI - R package to analyse intra-species and inter-species protein-protein interactions in the model plant Arabidopsis thaliana
Authors: Nussbaumer Thomas
Published: February 2019

Intra-species protein-protein interactions (PPI) provide valuable information about the systemic response of a model species when facing either abiotic and biotic stress conditions. Inter-species PPI can otherwise offer insights into how microbes interact with its host and can provide clues how early infection mechanism takes place. To understand these processes in a more comprehensive way and to compare it with experimental outcomes from omics studies, we require additional methods to analyse and visualize PPI data. We demonstrate the user-interface host_microbe_PPI that is implemented in R Shiny. It allows for interactively analysing inter-species and intra-species datasets from various published Arabidopsis thaliana datasets. It enables among other features comparisons of the centrality measurements (degree, betweenness and closeness) and analysis the existence of orthologous proteins in closely related genomes, e.g. when gene loss in host and non-host plants is compared. Arabidopsis was used even so the tool can be also applied in other host-microbe systems.
Associations between depth and micro-diversity within marine viral communities revealed through metagenomics
Authors: Coutinho FH , Rosselli R , Rodríguez-Valera F
Published: February 2019

Viruses are extremely abundant and diverse biological entities that contribute to the functioning of marine ecosystems. Despite their recognized importance no studies have addressed trends of micro-diversity in marine viral communities across depth gradients. To fill this gap we obtained metagenomes from both the cellular and viral fractions of Mediterranean seawater samples spanning the epipelagic to the bathypelagic zone at 15, 45, 60 and 2000 meters deep. The majority of viral genomic sequences obtained were derived from bacteriophages of the order Caudovirales, and putative host assignments suggested that they infect some of the most abundant bacteria in marine ecosystems such as Pelagibacter, Puniceispirillum and Prochlorococcus. We evaluated micro-diversity patterns by measuring the accumulation of synonymous and non-synonymous mutations in viral genes. Our results demonstrated that the degree of micro-diversity differs among genes encoding metabolic, structural, and replication proteins and that the degree of micro-diversity increased with depth. These trends of micro-diversity were linked to the changes in environmental conditions observed throughout the depth gradient, such as energy availability, host densities and proportion of actively replicating viruses. These observations allowed us to generate hypotheses regarding the selective pressures acting upon marine viruses from the epipelagic to the bathypelagic zones.
SWITCH 1/DYAD is a novel WINGS APART-LIKE antagonist that maintains sister chromatid cohesion in meiosis
Authors: Yang Chao , Hamamura Yuki , Sofroni Kostika , Böwer Franziska , Stolze Sara Christina , Nakagami Hirofumi , Schnittger Arp
Published: February 2019

Mitosis and meiosis both rely on cohesin, which embraces the sister chromatids and plays a crucial role for the faithful distribution of chromosomes to daughter cells. Prior to the cleavage by Separase at anaphase onset, cohesin is largely removed from chromosomes by the non-proteolytic action of WINGS APART-LIKE (WAPL), a mechanism referred to as the prophase pathway. To prevent the premature loss of sister chromatid cohesion, WAPL is inhibited in early mitosis by Sororin. However, Sororin homologs have only been found to function as WAPL inhibitors during mitosis in vertebrates and Drosophila. Here we show that SWITCH 1/DYAD defines a novel WAPL antagonist that acts in meiosis of Arabidopsis. Crucially, SWI1 becomes dispensable for sister chromatid cohesion in the absence ofWAPL.Despite the lack of any sequence similarities, we found that SWI1 is regulated and functions in a similar manner as Sororin hence likely representing a case of convergent molecular evolution across the eukaryotic kingdom.
Cold Vacuum Extracts of Double Cherry Blossom (Gosen-Sakura) Leaves Show Antitumor Activity
Authors: Shibato Junko , Takenoya Fumiko , Hirabayashi Takahiro , Kimura Ai , Iwasaki Yusuke , Toyota Yoko , Hori Motohide , Tamogami Shigeru , Rakwal Randeep , Shioda Seiji
Published: February 2019

The present research examines the possibility of finding bio-molecular compounds from the double cherry blossom (termed as ‘Gosen-Sakura’ of Gosen-city, Niigata-prefecture, Japan) leaves, which have been long used in the preparation of the traditional Japanese sweet (wagashi) – ‘sakura-mochi’. Based on its indicated anti-microbial properties historically, our study provides a new low temperature vacuum extraction method for extracting ‘near natural form of water soluble leaf (cell) extracts from the Gosen-Sakura, and demonstrates the presence of some ‘novel’ compound(s) with anti-tumor cell lines proliferation inhibitory affects through the MTT assay. To our knowledge, no reports exist on the sakura tree ‘leaf (cell) extracts’ inhibiting tumor cell line growth. We further examined and compared the effects of known compounds with anti-tumor activity, coumarin and benzyl alcohol with Gosen-Sakura leaf extract; results lead us to hypothesize that the Gosen-Sakura leaf extract contains substance(s) other than the above 2 known compounds, with antitumor effect. Additionally, we speculate on the underlying mechanism of action of the Gosen-Sakura leaf extract by targeting cell division at the point of DNA synthesis and causing apoptosis. In conclusion, we present scientific evidence on the presence of a certain ‘novel’ biomolecule(s), with anti-tumor activity, in the Gosen-Sakura leaf which has been long used as a Japanese – the ‘sakura-mochi’.
Analysis of immunological resistance to primary Mycobacterium tuberculosis infection in humans
Authors: Weiner January , Domaszewska Teresa , Donkor Simon , Hill Philip C. , Sutherland Jayne S.
Published: February 2019

Background

Despite recent advances in diagnosis and treatment, tuberculosis (TB) remains a major infectious disease killer in resource-poor settings. Strategies to prevent Mycobacterium tuberculosis (Mtb) infection are urgently required. By characterising natural protective immunity to Mtb infection we aimed to identify correlates of protection to guide vaccine development and other immune based therapies.

Methods

Two groups of Mtb-exposed contacts of TB patients were recruited in The Gambia and assessed for Mtb infection status using either tuberculin skin test (TST) reactivity at baseline and 3 months or QuantiFERON (QFT) reactivity at baseline and 6 months. For both groups, converters were defined as having a negative test at baseline and a positive one at follow-up, while those with a negative test at both time-points were defined as non-converters (Mtb resisters). Participants were analysed using RNA-sequencing and plasma Mtb proteome IgA and IgG arrays.

Results

Several genes were found to be differentially expressed at baseline between the groups prior to any signs of infection by current tests. Modular analysis revealed a distinct B cell gene signature in TST non-converters compared to converters (at q < 10-6, AUC > 0.7), which was only present in the most highly exposed group. Interestingly, when infection status was defined by QFT, enrichment of Type I IFN and antiviral gene signatures was observed. Plasma IgG and IgA antibody reactivity across the entire Mtb proteome showed the best differentiation in individuals with the highest exposure. An AUC of 1.0 (q<10-3) was observed for IgA reactivity to Rv0134 and an AUC of 0.98 for IgA reactivity to both Rv0629c and Rv2188c (all lower in TST non-converters). IgG reactivity to Rv3223c resulted in an AUC of 0.96 (q < 10-4) and was again lower in TST non-converters. The highest AUC for those with lower Mtb exposure were 0.84 (Rv2411c) for IgA and 0.83 (Rv2131c) for IgG.

Conclusions

These data provide insight into the early protective response to Mtb infection and possible avenues for novel therapeutic strategies to prevent Mtb infection.
Tuning network dynamics from criticality to the chaotic balanced state
Authors: Li Jingwen , Shew Woodrow L.
Published: February 2019

According to many experimental observations, neurons in cerebral cortex tend to operate in an asynchronous regime, firing independently of each other. In contrast, many other experimental observations reveal cortical population firing dynamics that are relatively coordinated and occasionally synchronous. These discrepant observations have naturally led to a lively debate surrounding discrepant hypotheses. A commonly hypothesized explanation of asynchronous firing is that excitatory and inhibitory neurons are precisely correlated, nearly canceling each other, resulting in the so-called ‘chaotic balanced state’. On the other hand, the ‘criticality’ hypothesis posits an explanation of the more coordinated state that also requires a certain balance of excitatory and inhibitory interactions. Both hypotheses claim the same qualitative mechanism - properly balanced excitation and inhibition. Thus, a natural question arises: how are the chaotic balanced state and criticality related, how do they differ? Here we propose an answer to this question based on investigation of a simple, network-level computational model. We show that the strength of inhibitory synapses relative to excitatory synapses can be tuned from weak to strong to generate a family of models that spans a continuum from ‘criticality’ to the ‘chaotic balanced state’. Our results bridge two long-standing competing hypotheses and offer a possible explanation of discrepant experimental observations: neuromodulatory mechanisms that tune the strength of excitatory and inhibitory synapses may tune cortical state from criticality to the balanced state, and to intermediate states between these extremes.

Author summary

What is the dynamical state of cerebral cortex? Are neurons mostly uncorrelated, firing asynchronously with each other? Are synchronous oscillations important? The answers to these questions have fundamental implications for how the cortical neural population encodes and processes information. Here we show that two possible scenarios - criticality and the chaotic balanced state - that are typically considered incompatible can be attained in the same network by maintaining a certain kind of balance, while tuning the strength of inhibition relative to excitation.
PROGRESSION OF AUTOANTIBODIES ANTI-GAD AND ANTI-IA2 IN TYPE 1A DIABETICS AGED OF 5 TO 21 YEARS IN CÔTE D’IVOIRE
Authors: Judith Trébissou Aïssé Florence , Yapo-Crezoit Chiayé Claire Antoinette , Sibailly Pascal , Sanogo Mamadou , Ankotché Amos , Kouassi Dinard , Thérèse Kouassi Marie , Masmoudi Hatem , Yapo Adou Francis
Published: February 2019

Background

Diabetes autoantibodies are indispensable markers of diabetes classification.

Objective

to research autoantibodies anti-GAD and anti-IA2 in type 1A diabetics (T1D) aged 5 to 21 years, and to follow the progression of these autoantibodies in T1D patients, in Côte d’Ivoire.

Methods

The study population composed of 28 T1D patients, aged 5 to 21 years. T1D were followed up in two diabetes care centers in Abidjan district, Endocrinology departments of U.H.C of Yopougon and Treichville. Anti-GAD and anti-IA2 autoantibodies were researched by ELISA.

Results

anti-GAD and anti-IA2 were present in T1D and their siblings. After 2 years of diabetes, the titer of the anti-GAD autoantibodies increased to the mean value of 677.10 ± 353.20 IU / ml. Then, a fall of the anti-GAD autoantibodies until the cancellation was observed from the 8th to the 9th with values of 117 IU / ml to 10.14 IU / ml. Anti-IA2 autoantibodies fall at 9th year of diabetes with a value of 55.10 IU / ml.

Conclusion

anti-GAD and anti-IA2 autoantibodies persist after 9 years of diabetes, causing total destruction over time of the pancreatic β-cell mass in patients from Côte d’Ivoire, leading them to the death.
The value of non-motor features and genetic variants of Parkinson’s disease for clustering Lewy body diseases
Authors: Lucas-Jiménez Olaia , Diez Ibai , Ojeda Natalia , Ibarretxe-Bilbao Naroa , Peña Javier , Tijero Beatriz , Galdós Marta , Murueta-Goyena Ane , Pino Rocío Del , Acera Marian , Gómez-Esteban Juan Carlos , Gabilondo Iñigo
Published: February 2019

Introduction

The use of non-motor Parkinson’s disease (PD) features and genetic PD variants for clustering analyses may refine the phenotypic classification of idiopathic Lewy body (LB) diseases.

Methods

One-hundred participants [n=7 E46K-SNCA (n=5 symptomatic and n=2 asymptomatic), n=4 PARK2, n=3 LRRK2, n=8 dementia with Lewy bodies (DLB), n=48 idiopathic PD (iPD), n=30 healthy controls (HC)] underwent a comprehensive evaluation of non-motor and motor PD features. Non-motor features were used to perform a hierarchical clustering analysis with patients and HC using a Scikit-learn toolkit.

Results

Clustering analysis suggested three clusters of subjects including Cluster 1 or “Normal-to-mild”: young iPD (< 60 years) classified together with most HC and the variable LB burden genetic PD variants (PARK2 and LRRK2) characterized by having normal-to-mild cognitive disabilities and mild-to-moderate motor disability with few axial symptoms; Cluster 2 or “Mild-to-moderate”: old iPD patients (>60 years) classified together with the lowest symptomatic E46K-SNCA, PARK2 carriers and HCs, characterizing by having mild-to-moderate cognitive and motor disabilities with few axial symptoms; and Cluster 3 or “Severe”: old iPD (>60 years) classified together with all DLB and the most symptomatic E46K-SNCA carriers, characterized by having severe pattern-specific cognitive disabilities (visual attention, perception, processing speed, memory and executive functions) and severe motor PD manifestations with marked axial symptoms.

Conclusions

Our study supports the potential value of incorporating genetic PD variants in data-driven iPD classification algorithms and the usefulness of non-motor PD features, especially visual cognition abnormalities, to facilitate the identification of aggressive LB diseases.
Honey bees, Apis mellifera, are important pollinators of the highbush blueberry variety Ventura despite the inability to sonicate
Authors: Martin Keanu , Anderson Bruce , Minnaar Corneile , de Jager Marinus
Published: February 2019

Animal-mediated pollination is an essential ecosystem service which over a third of the world’s agricultural crops depend on. Blueberry fruit production is highly dependent on pollinators and in their native range they are pollinated mostly by bumble bees (Bombus spp.). Demand for blueberries has increased in recent years due to their perceived health benefits. Consequently, blueberry cultivation has expanded well beyond their native range, including several regions where bumble bees are not present. In many areas, honey bees may be the only commercially available pollinators of blueberries because many countries ban the importation of bumble bees. This study aimed to determine the benefits of honey bee pollination on blueberry fruit quality and quantity for the variety Ventura by comparing yields of honey-bee-pollinated flowers to flowers where pollinators had been excluded. Honey bees significantly increased berry mass and diameter. Our results suggest that the presence of honey bee pollinators potentially increases revenue by approximately $864 501/ha in areas without bumble bees. We conclude that Ventura is reliably pollinated by honey bees, and that honey bee pollination may be a useful substitute for bumble bees in areas where bumble bees are absent. We also determined the extent to which blueberry yields could still be improved by comparing fruit quality and quantity under honey bee pollination to fruit quality and quantity achieved through ideal hand pollination. We found that blueberry yields may be still be significantly increased relative to ideal hand pollination and we discuss potential ways to improve the efficiency of honeybee pollination in the future. Additional research is required to study how beneficial honey bees are to fruit yield on varieties as the benefits of honey bees are likely to vary across different varieties.
Environmental pheromone and endocrine signals correct heterochronic developmental phenotypes caused by insufficient expression oflet-7family microRNAs inC. elegans
Authors: Ilbay Orkan , Ambros Victor
Published: February 2019

Adverse environmental conditions can affect rates of animal developmental progression and lead to temporary developmental quiescence (diapause), exemplified by the dauer larva stage of the nematodeCaenorhabditis elegans. Remarkably, patterns of cell division and temporal cell fate progression inC. eleganslarvae are not affected by changes in developmental trajectory. However, the underlying physiological and gene regulatory mechanisms that ensure robust developmental patterning despite substantial plasticity in developmental progression are largely unknown. Here, we report that diapause-inducing environmental pheromone and endocrine signals correct heterochronic developmental cell lineage defects caused by insufficient expression oflet-7family microRNAs inC. elegans.Two conserved endocrine signaling pathways, DAF-7/TGF-β and DAF-2/Insulin, that confer on the larva diapause/non-diapause alternative developmental trajectories, interact with the nuclear hormone receptor, DAF-12, to initiate and regulate a rewiring of the genetic circuitry controlling temporal cell fates. This rewiring includes: 1) repression of the DAF-12 ligand-activated expression oflet-7family microRNAs, and 2) engagement of a novel ligand-independent DAF-12 activity to downregulate the criticallet-7family target Hunchback-like-1 (HBL-1). This alternative HBL-1 downregulation program is responsible for correctinglet-7family insufficiency phenotypes and it requires the activities of certain heterochronic genes,lin-46, lin-4andnhl-2,that are previously associated with an altered genetic program in post-diapause animals. Our results show how environmental pheromones and endocrine signaling pathways can coordinately regulate both developmental progression and cell fate transitions inC. eleganslarvae under stress, so that the developmental schedule of cell fates remains unaffected by changes in developmental trajectory.
Functional ultrasound imaging of deep visual cortex in awake non-human primates
Authors: Kévin Blaize , Marc Gesnik , Fabrice Arcizet , Harry Ahnine , Ulisse Ferrari , Thomas Deffieux , Pierre Pouget , Frédéric Chavane , Mathias Fink , José-Alain Sahel , Mickael Tanter , Serge Picaud
Published: February 2019

Deep regions of the brain are not easily accessible to investigation at the mesoscale level in awake animals or humans. We have recently developed functional Ultrasound (fUS) imaging fUS imaging technique to uncover deep hemodynamic functional responses. Applying fUS imaging on two awake non-human primates performing a passive fixation task, we reconstructed their retinotopic maps down to the deep calcarine and lunate sulci on visual areas (V1, V2 and V3). These maps were acquired in a single hour session with very few stimuli presentation. The spatial resolution of the technology is illustrated by mapping of Ocular Dominance (OD) columns within superficial and deep layers of the primary visual cortex. These acquisitions showed that OD selectivity is mostly present in layer IV but with evidence also in layers II/III and V. The fUS imaging technology therefore provides a new mesoscale approach to map brain activities at high spatiotemporal resolution in awake subjects within the whole depth of the cortex.
Sensory lesioning induces microglial synapse elimination via ADAM10 and fractalkine signaling
Authors: Gunner Georgia , Cheadle Lucas , Johnson Kasey M. , Ayata Pinar , Badimon Ana , Mondo Erica , Nagy Aurel , Liu Liwang , Bemiller Shane M. , Kim Ki-Wook , Lira Sergio A. , Lamb Bruce T. , Tapper Andrew R. , Ransohoff Richard M. , Greenberg Michael E. , Schaefer Anne , Schafer Dorothy P.
Published: February 2019

Microglia rapidly respond to changes in neural activity and inflammation to regulate synaptic connectivity. The extracellular signals, particularly neuron-derived molecules, that drive these microglial functions at synapses remains a key open question. Here, whisker lesioning, known to dampen cortical activity, induces microglia-mediated synapse elimination. We show that this synapse elimination is dependent on the microglial fractalkine receptor, CX3CR1, but not complement receptor 3, signaling. Further, mice deficient in the CX3CR1 ligand (CX3CL1) also have profound defects in synapse elimination. Single-cell RNAseq then revealed thatCx3cl1is cortical neuron-derived and ADAM10, a metalloprotease that cleaves CX3CL1 into a secreted form, is upregulated specifically in layer IV neurons and microglia following whisker lesioning. Finally, inhibition of ADAM10 phenocopiesCx3cr1-/-andCx3cl1-/-synapse elimination defects. Together, these results identify novel neuron-to-microglia signaling necessary for cortical synaptic remodeling and reveal context-dependent immune mechanisms are utilized to remodel synapses in the mammalian brain.