bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intravital quantification of absolute cytoplasmic B cell calcium reveals dynamic signaling across B cell differentiation stages
Authors: Ulbricht Carolin , Leben Ruth , Rakhymzhan Asylkhan , Kirchhoff Frank , Nitschke Lars , Radbruch Helena , Niesner Raluca A , Hauser Anja E 
Published: December 2019

AbstractDevelopment, function and maintenance of lymphocytes largely depend upon the cellular mobilization and storage of Ca2+ions. In B lymphocytes, the absolute amount of calcium mobilized and retained after cell signaling remains unknown, athough it is a crucial part of their selection within germinal centers and differentiation into plasma cells. Here, we introduce the novel reporter mouse strain YellowCaB that expresses the genetically encoded calcium indicator TN-XXL in CD19+lymphocytes. The construct consists of the electrondonor fluorophore eCFP and the acceptor citrine, linked by a calcium sensitive domain. Its conformation and therefore donor quenching is directly linked to cytosolic calcium concentrations. By combining intravital two-photon fluorescence lifetime microscopy with our numerical approach for phasor-based analysis, we are able to extract absolute cytoplasmic calcium concentrations in activated B cells for the first timein vivo. We show that calcium concentrations in B cells are highly dynamic and fluctuations persist in extrafollicular B cells with functional relevance.
HIV corruption of the Arp2/3-Cdc42-IQGAP1 axis to hijack cortical F-Actin to promote cell-cell viral spread
Authors: Aggarwal Anupriya , Ospina Stella Alberto , Henry Catherine , Narayan Kedar , Turville Stuart G. 
Published: December 2019

AbstractF-Actin remodelling is important for the spread of HIV via cell-cell contacts, yet the mechanisms by which HIV corrupts the actin cytoskeleton are poorly understood. Through live cell imaging and focused ion beam scanning electron microscopy (FIB-SEM), we observed F-Actin structures that exhibit strong positive curvature to be enriched for HIV buds. Virion proteomics, gene silencing, and viral mutagenesis supported a Cdc42-IQGAP1-Arp2/3 pathway as the primary intersection of HIV budding, membrane curvature and F-Actin regulation. Whilst HIV egress activated the Cdc42-Arp2/3 filopodial pathway, this came at the expense of cell-free viral release. Importantly, release could be rescued by cell-cell contact, provided Cdc42 and IQGAP1 were present. From these observations we conclude that a proportion out-going HIV has corrupted a central F-Actin node that enables initial coupling of HIV buds to cortical F-Actin to place HIV at the leading cell edge. Whilst this initially prevents particle release, maturation of cell-cell contacts signals back to this F-Actin node to enable viral release & subsequent infection of the contacting cell.
HDAC inhibition ameliorates cone survival in retinitis pigmentosa mice
Authors: Samardzija Marijana , Corna Andrea , Gomez-Sintes Raquel , Jarboui Mohamed Ali , Armento Angela , Roger Jerome E. , Petridou Eleni , Haq Wadood , Paquet-Durand Francois , Zrenner Eberhart , Zeck Günther , Grimm Christian , Boya Patricia , Ueffing Marius , Trifunović Dragana 
Published: December 2019

AbstractCone photoreceptor cell death in inherited retinal diseases, such as Retinitis Pigmentosa (RP), leads to the loss of high acuity and color vision and ultimately to blindness. In RP, a vast number of mutations perturb the structure and function of rod photoreceptors while cones remain initially unaffected. Cone death follows rod death secondarily due to increased oxidative stress, inflammation, and loss of structural and nutritional support provided by rods. Here, we show that secondary cone cell death in animal models for RP was associated with an increased activity of histone deacetylates (HDACs). A single intravitreal injection of an HDAC inhibitor at a late stage of the disease, when majority of rods have already degenerated, was sufficient to delay cone death and support long-term cone survival. Moreover, the surviving cones remained light sensitive and initiated light-driven ganglion cell responses. RNA-seq analysis of protected cones demonstrated that HDAC inhibition led to multi-level protectionviaregulation of different pro-survival pathways, including MAPK, PI3K-Akt, and autophagy. This study suggests a unique possibility for a targeted pharmacological protection of both primary degenerating rods and secondary dying cones by HDAC inhibition and creates hope to maintain vision in RP patients independent of the disease stage.
Epigenetically bistable regions across neuron-specific genes govern neuron eligibility to a coding ensemble in the hippocampus
Authors: Odell S. C. , Taki F. , Klein S. , Chen R. J. , Levine O. B. , Skelly M.J. , Nabila A. , Brindley E. , Gal Toth J. , Dündar F. , Sheridan C. K. , Fetcho R. N. , Alonso A. , Liston C. , Landau D. A. , Pleil K. E , Toth M. 
Published: December 2019

SummaryEpisodic memories are stored in distributed neurons but how eligibility of individual neurons to coding ensembles is determined remains elusive. We identified thousands of predominantly bistable (CpG methylated or unmethylated) regions within neuronal gene bodies, established during the development of the mouse hippocampal dentate gyrus. Reducing DNA methylation and the proportion of the methylated epialleles at bistable regions compromised novel context-induced neuronal activation and spatial memory. Conversely, increasing methylation and the frequency of the methylated epialleles at bistable regions enhanced intrinsic excitability and spatial memory but impaired spatial working memory, indicating that the developmentally established methylated-unmethylated epiallelic balance at bistable regions is essential for proper neuronal excitability and hippocampal cognitive functions. Single-nucleus profiling revealed the enrichment of specific epialleles from a subset of bistable regions, primarily exonic, in encoding neurons. We propose a model in which epigenetically bistable regions create neuron heterogeneity, and specific constellations of exonic epialleles dictate, via modulating neuronal excitability, eligibility to a coding ensemble.
Estimates of abundance and change in abundance of the Indo-Pacific bottlenose dolphins (Tursiops aduncus) along the south coast of South Africa
Authors: Vargas-Fonseca OA , Kirkman SP , Oosthuizen WC , Bouveroux T , Cockcroft V , Conry D , Pistorius PA 
Published: December 2019

AbstractWe investigated the abundance of Indo-Pacific bottlenose dolphins (Tursiops aduncus) along the south coast of South Africa, from the Goukamma Marine Protected Area (MPA) to the Tsitsikamma MPA, between 2014 and 2016. During this period, 662.3h of boat-based photo-identification survey effort was carried out, and the sighting histories of 817 identified individuals were used to estimate abundance using mark-recapture modelling. The selected open population model (POPAN) provided an estimate of 2,295 individuals (95% CI: 1,157-4,553) for the entire study area. A model estimate was produced for a subset of the study area, Plettenberg Bay, which could be compared with a past estimate for this location (2002-2003). The comparison suggested a 72.3% decrease in abundance, from 6,997 (95% CI: 5,230-9,492) in 2002-2003 to 1,940 (95% CI: 1,448-2,600) in 2014-2016. The decline in abundance was supported by a 72% reduction in mean group size for Plettenberg Bay between the periods. It is essential to be able to assess abundance changes at other locations to inform revision ofT. aduncusconservation status in South Africa.
Overprecision Increases Subsequent Surprise
Authors: Schatz Derek , Moore Don A. 
Published: December 2019

AbstractOverconfident people should be surprised that they are so often wrong. Are they? Three studies examined the relationship between confidence and surprise in order to shed light on the psychology of overprecision in judgment. Participants reported ex-ante confidence in their beliefs, and after receiving accuracy feedback, they then reported ex-post surprise. Results show that more ex-ante confidence produces less ex-post surprise for correct answers; this relationship reverses for incorrect answers. However, this sensible pattern only holds for some measures of confidence; it fails for confidence-interval measures. The results can help explain the robust durability of overprecision in judgment.
Anillin/Mid1p interacts with the ECSRT-associated protein Vps4p and mitotic kinases to regulate cytokinesis in fission yeast
Authors: Rezig Imane M. , Gould Gwyn W. , McInerny Christopher J. 
Published: December 2019

AbstractCytokinesis is the final stage of the cell cycle which separates cellular constituents to produce two daughter cells. UsingSchizosaccharomyces pombewe have investigated the role of various classes of proteins involved in this process. Central to these is anillin/Mid1p which forms a ring-like structure at the cell equator that predicts the site of cell separation through septation in fission yeast. Here we demonstrate a direct physical interaction between Mid1p and the endosomal sorting complex required for transport (ESCRT)-associated protein Vps4p. The interaction is essential for cell viability, and Vps4p is required for the correct cellular localization of Mid1p. Furthermore, we show that Mid1p is phosphorylated by the aurora kinase Aurora A, that the interaction ofmid1andark1genes is essential for cell viability, and that Ark1p is also required for the correct cellular localization of Mid1p. We mapped the sites of phosphorylation of Mid1p by Aurora A and the polo kinase Plk1 and assessed their importance by mutational analysis. Mutational analysis revealed S332, S523 and S531 to be required for Mid1p function and its interaction with Vps4p, Ark1p and Plo1p. Combined our data suggest a physical interaction between Mip1p and Vps4p important for cytokinesis, and identify phosphorylation of Mid1p by aurora and polo kinases as being significant for this process.Author summaryReplication is a property of all living cells, with cell separation, so-called cytokinesis, the final step in the process. A large number of proteins have been identified that are required for cytokinesis, but in many cases it is not understand how they interact and regulate each other. In this research we have analysed two classes of proteins founds in all eukaryotic cells with central roles in cytokinesis: the endosomal sorting complex required for transport (ESCRT) proteins and the anillin protein Mid1p. We identify a direct physical interaction between the ESCRT protein Vps4 and anillin/Mid1p, and explore how it regulates cytokinesis. Midp1 activity is shown to controlled by the protein kinase Ark1p by direct phosphorylation, and this phosphorylation is important for Mid1p function. These observations identify new ways in which ESCRT and anillin/Mid1p control cell separation.
Investigations into the declining health of alder (Alnus glutinosa) along the river Lagan in Belfast, including the first report ofPhytophthora lacustriscausing disease ofAlnusin Northern Ireland
Authors: Hanlon Richard O , Wilson Julia , Cox Deborah 
Published: December 2019

AbstractCommon alder (Alnus glutinosa) is an important tree species, especially in riparian and wet habitats. Alder is very common across Ireland and Northern Ireland, and provides a wide range of ecosystem services. Surveys along the river Lagan in Belfast, Northern Ireland led to the detection of several diseasedAlnustrees. As it is known that Alnus suffers from aPhytophthorainduced decline, this research set out to identify the presence and scale of the risk toAlnushealth fromPhytophthoraand other closely related oomycetes. Sampling and a combination of morphological and molecular testing of symptomatic plant material and river baits identified the presence of severalPhytophthoraspecies, includingPhytophthora lacustris. A survey of the tree vegetation along an 8.5 km stretch of the river revealed that of the 166Alnustrees counted, 28 were severely defoliated/diseased and 9 were dead. Inoculation studies using pottedAlnussaplings demonstrate thatP. lacustriswas able to cause disease, and Koch’s postulates for this pathogen-host combination were completed, which suggests a future risk toAlnushealth fromP. lacustrisin Northern Ireland.
Prevalence, risk factors and health seeking behaviour of pulmonary tuberculosis in four tribal dominated districts of Odisha: comparison with studies in other regions of India
Authors: Hussain Tahziba , Tripathy Sushri Shanta , Das Shritam , Das Dasarathi , Thomas Beena 
Published: December 2019

AbstractAimTo determine the prevalence of pulmonary tuberculosis, socio-cultural practices and health seeking behaviour of tribal people in four districts of Odisha.MethodologyThis was an action research study with qualitative and quantitative design following a sequential approach implemented in a 4-phased manner. It was carried out in the 6 selected villages from July,2015 to June,2017. The screening for active TB among chest symptomatics is followed as per the guidelines of the (RNTCP) Revised National Tuberculosis Control Program in India.ResultsIn all, 1455 households were surveyed in the 6 tribal dominated villages of 4 districts, namely Balangir, Dhenkanal, Kandhmal and Mayurbhanj. Total population of the villages was 6681. Based on the eligibility, 5144 (97.7%) individuals were screened. About 139 (2.3%) could not be screened due to non-availability in their households during day time. Out of these, 126 chest symptomatic individuals were identified. Sputum samples were collected from these and sent to the National Reference Laboratory, RMRC, Bhubaneswar using public transport and maintaining cold chain. 35 patients were found to be having active TB disease. 18 were culture positive. The prevalence of pulmonary TB is 0.68%. The risk factors seemed to be ignorance about TB symptoms, addiction to alcoholic drinks, difficulty reaching the health facilities owing to the long distances, lack of communication and transport. In addition, other morbidities like Malaria, diabetes, hypertension, malnutrition, etc. were observed in the tribes of the study sites.ConclusionObserved prevalence suggests further strengthening of TB control program. This study is the first of its kind in this State.
Long-range quantum coherence of the photosystem 2 complexes in living cyanobacteria
Authors: Rammler T. , Wackenhut F. , Oven-Krockhaus S. zur , Rapp J. , Forchhammer K. , Harter K. , Meixner A. J. 
Published: December 2019

AbstractThe first step in photosynthesis is an extremely efficient energy transfer mechanism, which is difficult to be explained by classical short-range energy migration (“hopping”) and led to the debate to which extent quantum coherence is involved in the energy transfer between the photosynthetic pigments. Embedding living cyanobacteria between the mirrors of an optical microresonator and using low intensity white light irradiation we observe vacuum Rabi splitting in the transmission and fluorescence spectra as a result of strong light matter coupling of the chlorophyll and the resonator modes. The Rabi-splitting scales with the number of chlorophyll a pigments involved in coherent coupling indicating forming a polaritonic state which is delocalized over the entire cyanobacterial thylakoid system, down to the single photon level. Our data provide evidence that a delocalized polaritonic state is the basis of the extremely high energy transfer efficiency under natural conditions.
Unconventional kinetochore kinases KKT2 and KKT3 have unique centromere localization domains
Authors: Marcianò Gabriele , Ishii Midori , Nerusheva Olga O. , Akiyoshi Bungo 
Published: December 2019

AbstractChromosome segregation in eukaryotes is driven by the kinetochore, the macromolecular protein complex that assembles onto centromeric DNA and binds spindle microtubules. Cells must tightly control the number and position of kinetochores so that all chromosomes assemble a single kinetochore. A central player in this process is the centromere-specific histone H3 variant CENP-A, which localizes constitutively at centromeres and promotes kinetochore assembly. However, CENP-A is absent from several eukaryotic lineages including kinetoplastids, a group of evolutionarily divergent eukaryotes that have an unconventional set of kinetochore proteins. There are six proteins that localize constitutively at centromeres in the kinetoplastid parasiteTrypanosoma brucei,among which two homologous protein kinases (KKT2 and KKT3) have limited similarity to polo-like kinases. In addition to the N-terminal kinase domain and the C-terminal divergent polo boxes, KKT2 and KKT3 have a central domain of unknown function as well as putative DNA-binding motifs. Here we show that KKT2 and KKT3 are important for the localization of several kinetochore proteins and that their central domains are sufficient for centromere localization inT. brucei. Crystal structures of the KKT2 central domain from two divergent kinetoplastids reveal a unique zinc-binding domain (termed the CL domain for centromere localization), which promotes its kinetochore localization inT. brucei. Mutations in the equivalent domain in KKT3 abolish its kinetochore localization and function. Our work shows that the unique central domains play a critical role in mediating the centromere localization of KKT2 and KKT3.
Quantification of guanosine tetraphosphate and other nucleotides in plants and algae using stable isotope-labelled internal standards
Authors: Bartoli Julia , Citerne Sylvie , Mouille Gregory , Bouveret Emmanuelle , Field Ben 
Published: December 2019

AbstractGuanosine tetraphosphate (G4P) and guanosine pentaphosphate (G5P) are signalling nucleotides found in bacteria and photosynthetic eukaryotes that are implicated in a wide-range of processes including stress acclimation, developmental transitions and growth control. Measurements of G4P/G5P levels are essential for studying the diverse roles of these nucleotides. However, G4P/G5P quantification is particularly challenging in plants and algae due to lower cellular concentrations, compartmentation and high metabolic complexity. Despite recent advances the speed and accuracy of G4P quantification in plants and algae can still be improved. Here, we report a new approach for rapid and accurate G4P quantification, applicable to plants and algae, which relies on the use of synthesised stable isotope-labelled as internal standards. We anticipate that this approach will accelerate research into the function of G4P signaling in plants, algae and other organisms.
A unified circuit model of attention: Neural and behavioral effects
Authors: Lindsay Grace W. , Rubin Daniel B. , Miller Kenneth D. 
Published: December 2019

AbstractSelective visual attention modulates neural activity in the visual system in complex ways and leads to enhanced performance on difficult visual tasks. Here, we show that a simple circuit model, the stabilized supralinear network, gives a unified account of a wide variety of effects of attention on neural responses. We replicate results from studies of both feature and spatial attention, addressing findings in a variety of experimental paradigms on changes both in firing rates and in correlated neural variability. Finally, we expand this circuit model into an architecture that can perform visual tasks—a convolutional neural network—in order to show that these neural effects can enhance detection performance. This work provides the first unified mechanistic account of the effects of attention on neural and behavioral responses.
Representation of semantic information in ventral areas during encoding is associated with improved visual short-term memory
Authors: Stojanoski Bobby , Emrich Stephen M. , Cusack Rhodri 
Published: December 2019

AbstractWe rely upon visual short-term memory (VSTM) for continued access to perceptual information that is no longer available. Despite the complexity of our visual environments, the majority of research on VSTM has focused on memory for lower-level perceptual features. Using more naturalistic stimuli, it has been found that recognizable objects are remembered better than unrecognizable objects. What remains unclear, however, is how semantic information changes brain representations in order to facilitate this improvement in VSTM for real-world objects. To address this question, we used a continuous report paradigm to assess VSTM (precision and guessing rate) while participants underwent functional magnetic resonance imaging (fMRI) to measure the underlying neural representation of 96 objects from 4 animate and 4 inanimate categories. To isolate semantic content, we used a novel image generation method that parametrically warps images until they are no longer recognizable while preserving basic visual properties. We found that intact objects were remembered with greater precision and a lower guessing rate than unrecognizable objects (this also emerged when objects were grouped by category and animacy). Representational similarity analysis of the ventral visual stream found evidence of category and animacy information in anterior visual areas during encoding only, but not during maintenance. These results suggest that the effect of semantic information during encoding in ventral visual areas boosts visual short-term memory for real-world objects.
Enhanced prediction of cognitive function using aging-sensitive networks within the human structural connectome
Authors: Madole James W. , Ritchie Stuart J. , Cox Simon R. , Buchanan Colin R. , Hernández Maria Valdés , Maniega Susana Muñoz , Wardlaw Joanna M. , Harris Mat A. , Bastin Mark E. , Deary Ian J. , Tucker-Drob Elliot M. 
Published: December 2019

AbstractUsing raw structural and diffusion brain MRI data from the UK Biobank (UKB;N= 3,155, ages 45-75 years) and the Lothian Birth Cohort 1936 (LBC1936;N= 534, all age 73 years), we examine aging of regional grey matter volumes (nodes) and white matter structural connectivity (edges) within networks-of-interest in the human brain connectome. In UKB, the magnitude of age-differences in individual node volumes and edge weights corresponds closely with their loadings on their respective principal components of connectome-wide integrity (|rnodes| = 0.459; |redges| = 0.595). In LBC1936, connectome-wide and subnetwork-specific composite indices of node integrity were predictive of processing speed, visuospatial ability, and memory, whereas composite indices of edge integrity were associated specifically with processing speed. Childhood IQ was associated with greater node integrity at age 73. However, node and edge integrity remained associated with age 73 cognitive function after controlling for childhood IQ. Adult connectome integrity is therefore both a marker of early-life cognitive function and a substrate of late-life cognitive aging.
Origin Specific Genomic Selection: a simple process to optimize the favourable contribution of parents to progeny
Authors: Yang Chin Jian , Sharma Rajiv , Gorjanc Gregor , Hearne Sarah , Powell Wayne , Mackay Ian 
Published: December 2019

AbstractModern crop breeding is in constant demand for new genetic diversity as part of the arms race with genetic gain. The elite gene pool has limited genetic variation and breeders are trying to introduce novelty from unadapted germplasm, landraces and wild relatives. For polygenic traits, currently available approaches to introgression are not ideal, as there is a demonstrable bias against exotic alleles during selection. Here, we propose a partitioned form of genomic selection, called Origin Specific Genomic Selection (OSGS), where we identify and target selection on favourable exotic alleles. Briefly, within a population derived from a bi-parental cross, we isolate alleles originating from the elite and exotic parents, which then allows us to separate out the predicted marker effects based on the allele origins. We validated the usefulness of OSGS using two nested association mapping (NAM) datasets: barley NAM (elite-exotic) and maize NAM (elite-elite), as well as by computer simulation. Our results suggest that OSGS works well in bi-parental crosses, and it is possible to extend the approach to broader multi-parental populations.