bluuebunny/crossref_metadata_2025 huggingface dataset:
High photon count rates improve the quality of super-resolution fluorescence fluctuation spectroscopy
Authors: Schneider Falk , Hernandez-Varas Pablo , Lagerholm B. Christoffer , Shrestha Dilip , Sezgin Erdinc , Roberti M. Julia , Ossato Giulia , Hecht Frank , Eggeling Christian , Urbančič Iztok
Published: September 2019

Probing the diffusion of molecules has become a routine measurement across the life sciences, chemistry and physics. It provides valuable insights into reaction dynamics, oligomerisation, molecular (re-)organisation or cellular heterogeneities. Fluorescence correlation spectroscopy (FCS) is one of the widely applied techniques to determine diffusion dynamics in two and three dimensions. This technique relies on the temporal autocorrelation of intensity fluctuations but recording these fluctuations has thus far been limited by the detection electronics, which could not efficiently and accurately time-tag photons at high count rates. This has until now restricted the range of measurable dye concentrations, as well as the data quality of the FCS recordings, especially in combination with super-resolution stimulated emission depletion (STED) nanoscopy.

Here, we investigate the applicability and reliability of (STED-)FCS at high photon count rates (average intensities of up to 40 MHz) using novel detection equipment, namely hybrid detectors and real-time gigahertz sampling of the photon streams implemented on a commercial microscope. By measuring the diffusion of fluorophores in solution and cytoplasm of live cells, as well as in model and cellular membranes, we show that accurate diffusion and concentration measurements are possible in these previously inaccessible high photon count regimes. Specifically, it offers much greater flexibility of experiments with biological samples with highly variable intensity, e.g. due to a wide range of expression levels of fluorescent proteins. In this context, we highlight the independence of diffusion properties of cytosolic GFP in a concentration range of approx. 0.01–1 μM. We further show that higher photon count rates also allow for much shorter acquisition times, and improved data quality. Finally, this approach also pronouncedly increases the robustness of challenging live cell STED-FCS measurements of nanoscale diffusion dynamics, which we testify by confirming a free diffusion pattern for a fluorescent lipid analogue on the apical membrane of adherent cells.
OPETH: Open Source Solution for Real-time Peri-event Time Histogram Based on Open Ephys
Authors: Széll András , Martínez-Bellver Sergio , Hegedüs Panna , Hangya Balázs
Published: September 2019

Single cell electrophysiology remains one of the most widely used approaches of systems neuroscience. Real-time feedback during electrophysiology experiments is important to guide experimental decisions that eventually determine the quality of recording, duration of the project and value of the collected data. We present an open-source tool that enables flexible online visualization of action potential alignment to external events, called the peri-event or peristimulus time histogram (OPETH). Based on the Open Ephys open source data acquisition system, we developed a Python interface for real-time plotting of neuronal spike times and evoked waveforms with respect to external events represented by digital logic signals. These digital inputs may signal photostimulation time stamps for in vivo optogenetic identification of cell types or the times of behaviorally relevant events during in vivo behavioral neurophysiology experiments. Therefore, OPETH allows real-time identification of genetically defined neuron types or behaviorally responsive populations. By allowing ‘hunting’ for neurons of interest, OPETH may significantly increase the efficiency of experiments that combine in vivo electrophysiology with behavior or optogenetic tagging of neurons.
Distances walked by beach users and protecting shorebird habitat zones from disturbance
Authors: Totterman Stephen
Published: September 2019

Human population growth along Australia’s coast is increasing development and recreation pressures on beaches and shorebirds. This study observed human recreation on 18 beaches on the far north coast of New South Wales in February and March 2019. The far north coast supports the largest numbers of beach-resident Australian Pied Oystercatchers Haematopus longirostris in the State. The most frequent activities observed were walking (29%), dog walking (21%) and swimming (16%). Walkers covered greater distances compared to other beach users. For beach walkers and dog walkers combined, the mean along shore distance walked from an access point was 809 m and the 95th percentile was 1990 m. Noting that human recreation disturbance is a major conservation threat to beach nesting birds and that pro-environmental behaviour is uncommon among beach users, large separation distances between beach access points and shorebird habitat zones are recommended to reduce human intrusions into those zones. This spatial zoning and passive human exclusion strategy can be applied to long and less-developed beaches.
The Manganese Salt (MnJ) Functions as A Potent Universal Adjuvant
Authors: Zhang Rui , Wang Chenguang , Guan Yukun , Wei Xiaoming , Sha Mengyin , Jing Miao , Lv Mengze , Xu Jing , Wan Yi , Jiang Zhengfan
Published: September 2019

Aluminum adjuvants have been used for a century in various vaccines due to its ability to potentiate humoral immunity and safety records since 1920s. Manganese is an essential micronutrient required for diverse biological activities in cells. We previously found that Mn2+ is a strong type I-interferon stimulator activating the cGAS-STING pathway. Herein we report that a colloidal manganese salt (MnJ) is a potent adjuvant to induce both humoral and cellular immune responses, particularly CTL activation. When administrated intranasally, MnJ was also a strong mucosal adjuvant, inducing high levels of IgA antibodies. MnJ strongly promoted dendritic cell maturation and antigen-specific T cell activation. Interestingly, IL-1/-18 induction and release by Mn2+-activated ASC-mediated inflammasomes were not observed. MnJ showed great adjuvant effects to all tested antigens including inactivated viruses, recombinant proteins and peptides by either intramuscular or intranasal immunization. These findings may have implications in developing potent but safe Mn2+-containing vaccines.
Benthic jellyfish dominate water mixing in mangrove ecosystems
Authors: Durieux David M. , Du Clos Kevin T. , Gemmell Brad J.
Published: September 2019

Water mixing is a critical mechanism in marine habitats that governs many important processes, including nutrient transport. Physical mechanisms, such as winds or tides, are primarily responsible for mixing effects in shallow coastal systems, but the sheltered habitats adjacent to mangroves experience very low turbulence and vertical mixing. The significance of biogenic mixing in pelagic habitats has been investigated but remains unclear. In this study we show that the upside-down jellyfish Cassiopea sp. plays a significant role with respect to biogenic contributions to water column mixing within its shallow natural habitat (< 2 m deep). The mixing contribution was determined by means of high-resolution flow velocimetry methods in both the laboratory and in the natural environment. We demonstrate that Cassiopea sp. continuously pumps water from the benthos upward in a vertical jet with flow velocities on the scale of centimeters per second. The volumetric flow rate was calculated to be 212 l h−1 for average sized animals (8.6 cm bell diameter), which translates to turnover of the entire water column every 15 minutes for a median population density (29 animals m−2). In addition, we found Cassiopea sp. are capable of releasing porewater into the water column at an average rate of 2.64 ml h−1 per individual. The release of nutrient-rich benthic porewater combined with strong contributions to water column mixing, suggest a role for Cassiopea sp. as an ecosystem engineer in mangrove habitats.

Significance Statement

Water mixing is a critical process for aquatic life. Coastal mangrove habitats are vital nurseries for commercially and ecologically important species, but these sheltered habitats experience little water mixing. The upside-down jellyfish, Cassiopea sp., occurs in circumtropical mangrove habitats at high densities. They are epibenthic and pulse nearly continuously, producing a vertical current that transports hundreds of liters of seawater per hour. This results in turnover of the entire water column every 15 minutes for an average population. Additionally, Cassiopea sp. can greatly expedite the transport of nutrient-rich water from sediments into the water column. Thus, Cassiopea sp. represents a previously unrecognized ecosystem engineer that can affect primary productivity, nutrient distribution, and alter new habitats as their range is expanding.
Molecular Atlas of the Adult Mouse Brain
Authors: Ortiz Cantin , Navarro Jose Fernandez , Jurek Aleksandra , Märtin Antje , Lundeberg Joakim , Meletis Konstantinos
Published: September 2019

Brain maps are essential for integrating information and interpreting the structure-function relationship of circuits and behavior. We aimed to generate a systematic classification of the adult mouse brain organization based on unbiased extraction of spatially-defining features. Applying whole-brain spatial transcriptomics, we captured the gene expression signatures to define the spatial organization of molecularly discrete subregions. We found that the molecular code contained sufficiently detailed information to directly deduce the complex spatial organization of the brain. This unsupervised molecular classification revealed new area- and layer-specific subregions, for example in isocortex and hippocampus, and a new division of striatum. The whole-brain molecular atlas further supports the identification of the spatial origin of single neurons using their gene expression profile, and forms the foundation to define a minimal gene set - a brain palette – that is sufficient to spatially annotate the adult brain. In summary, we have established a new molecular atlas to formally define the identity of brain regions, and a molecular code for mapping and targeting of discrete neuroanatomical domains.
Regulation of BMP Signaling by O-GlcNAcylation
Authors: Moulton Matthew , Humphreys Greg , Kim Alexander , Letsou Anthea
Published: September 2019

Precise regulation of signal transduction is critical throughout organismal life, both for embryonic development and for adult homeostasis. To ensure proper spatio-temporal signal transduction, Bone Morphogenetic Protein (BMP) signaling pathways, like all other signaling pathways, are regulated by both agonists and antagonists. Here, we report identification of a previously unrecognized method of signal antagonism for Dpp (Decapentaplegic), aDrosophilaBMP family member. We demonstrate that the BMP type I receptor Saxophone (Sax) functions as a Dpp receptor in theDrosophilaembryonic epidermis, but that its activity is normally inhibited by the O-linked glycosyltransferase Super sex combs (Sxc). In wild-type embryos, inhibition of Saxophone (Sax) activity in the epidermis marks the BMP type I receptor Thickveins (Tkv) as the sole conduit for Dpp. In contrast, insxcmutants, the Dpp signal is transduced by both Tkv and Sax, and elevated Dpp signaling induces errors in embryonic development that lead to embryonic death. We also demonstrate that Sax is the O-glycosylated target of Sxc and that O-glycosylation of Sax can be modulated by dietary sugar. Together, these findings link fertility to nutritive environment and point to Sax (activin receptor-like kinase 2 [ACVR1 or ALK2]) signaling as the nutrient-sensitive branch of BMP signaling.

Graphical Abstract
A Missense Point Mutation in Nerve Growth Factor (NGFR100W) Results in Selective Peripheral Sensory Neuropathy
Authors: Yang Wanlin , Sung Kijung , Xu Wei , Rodriguez Maria J , Wu Andrew C. , Santos Sarai A. , Fang Savannah , Uber Rebecca K. , Dong Stephanie X. , Guillory Brandon C. , Orain Xavier , Raus Jordan , Jolivalt Corrine , Calcutt Nigel , Rissman Robert A. , Ding Jianqing , Wu Chengbiao
Published: September 2019

A missense point mutation in nerve growth factor (NGFR100W) is associated with hereditary sensory autonomic neuropathy V (HSAN V), originally discovered in a Swedish family. These patients develop severe loss of perception to deep pain but with apparently normal cognitive functions. To better understand the disease mechanism, we have generated the first NGFR100Wknockin mouse model of HSAN V. Mice homozygous for the NGFR100Wmutation (NGFfln/fln) showed significant structural deficits in intra-epidermal nerve fibers (IENFs) at birth. These mice had a total loss of pain perception at ∼2 months of age and they often failed to survive to full adulthood. Heterozygous mice (NGF+/fln) developed a progressive degeneration of small sensory fibers both behaviorally and functionally: they showed a progressive loss of IENFs starting at the age of 9 months accompanied with progressive loss of perception to painful stimuli such as noxious temperature. Quantitative analysis of lumbar 4/5 dorsal root ganglia (DRG) revealed a significant reduction in small size neurons positive for calcitonin gene-related peptide, while analysis of sciatic nerve fibers revealed the mutant NGF+/flnmice had no reduction in myelinated nerve fibers. Significantly, the amount of NGF secreted from fibroblasts were reduced in heterozygous and homozygous mice compared to their wild-type littermates. Interestingly, NGF+/flnshowed no apparent structural alteration in the brain: neither the anterior cingulate cortex nor the medial septum including NGF-dependent basal forebrain cholinergic neurons. Accordingly, these animals did not develop appreciable deficits in tests for central nervous system function. Our study provides novel insights into the selective impact of NGFR100Wmutation on the development and function of the peripheral sensory system.
The role of 3’UTR-protein complexes in the regulation of protein multifunctionality and subcellular localization
Authors: Ribeiro Diogo M. , Prod’homme Alexis , Teixeira Adrien , Zanzoni Andreas , Brun Christine
Published: September 2019

Multifunctional proteins often perform their different functions when localized in different subcellular compartments. However, the mechanisms leading to their localization are largely unknown. Recently, 3’UTRs were found to regulate the cellular localization of newly synthesized proteins through the co-translational formation of 3’UTR-protein complexes. Here, we investigate the formation of 3’UTR-protein complexes involving multifunctional proteins by exploiting large-scale protein-protein and protein-RNA interaction networks. Focusing on 238 human ‘extreme multifunctional’ (EMF) proteins, we predicted 1411 3’UTR-protein complexes involving 128 EMF proteins and evaluated their role in regulating protein cellular localization and multifunctionality. Notably, we find that EMF proteins lacking localization addressing signals, yet present at both the nucleus and cell surface, often form 3’UTR-protein complexes. In addition, they provide EMF proteins with the diversity of interaction partners necessary to their multifunctionality. Archetypal moonlighting proteins are also predicted to form 3’UTR-protein complexes thereby reinforcing our findings. Finally, our results indicate that the formation of 3’UTR-protein complex may be a common phenomenon in human cells, affecting up to 20% of the proteins in the human interactome.
FMRP promotes RNA localization to neuronal projections through interactions between its RGG domain and G-quadruplex RNA sequences
Authors: Goering Raeann , Hudish Laura I. , Guzman Bryan B. , Raj Nisha , Bassell Gary J. , Russ Holger A. , Dominguez Daniel , Taliaferro J. Matthew
Published: September 2019

The sorting of RNA molecules to distinct subcellular locations facilitates the activity of spatially restricted processes through local protein synthesis. This process affects thousands of transcripts yet precisely how these RNAs are trafficked to their destinations remains generally unclear. Here we have analyzed subcellular transcriptomes of FMRP-null mouse neuronal cells to identify transcripts that depend on FMRP for efficient transport to neurites. We found that these FMRP RNA localization targets contain a large enrichment of G-quadruplex sequences, particularly in their 3′ UTRs, suggesting that FMRP recognizes these sequences to promote the localization of transcripts that contain them. Fractionation of neurons derived from human Fragile X Syndrome patients revealed a high degree of conservation in the identity of FMRP localization targets between human and mouse as well as an enrichment of G-quadruplex sequences in human FMRP RNA localization targets. Using high-throughput RNA/protein interaction assays and single-molecule RNA FISH, we identified the RGG domain of FMRP as important for both interaction with G-quadruplex RNA sequences and the neuronal transport of G-quadruplex-containing transcripts. Finally, we used ribosome footprinting to identify translational regulatory targets of FMRP. The translational regulatory targets were not enriched for G-quadruplex sequences and were largely distinct from the RNA localization targets of FMRP, indicating that the two functions can be biochemically separated and are mediated through different target recognition mechanisms. These results establish a molecular mechanism underlying FMRP-mediated neuronal RNA localization and provide a framework for the elucidation of similar mechanisms governed by other RNA-binding proteins.
Information use in foraging flocks of songbirds - no evidence for social transmission of patch quality
Authors: Hillemann F. , Cole E. F. , Sheldon B. C. , Farine D. R.
Published: September 2019

Animals use behavioural cues from others to make decisions in a variety of contexts. There is growing evidence, from a range of taxa, that information about the locations of food patches can spread through a population via social connections. However, it is not known whether information about the quality of potential food sources transmits similarly. We studied foraging behaviour in a population of wild songbirds with known social associations, and tested whether flock members use social information about the profitability of patches to inform their foraging decisions. We provided artificial patches (ephemeral bird feeders) that appeared identical but were either profitable (contained food) or unprofitable (contained no food). If information about patch profitability spreads via social associations, we predicted that empty feeders would only be sampled by individuals that are less connected to each other than expected by chance. In contrast, we found that individuals recorded at empty feeders were more closely associated with each other than predicted by a null model simulating random arrival of individuals, mirroring pattern of increased connectedness among individuals recorded at full feeders. We then simulated arrival under network-based diffusion of information, and demonstrate that the observed pattern at both full and empty feeders matches predictions derived from this post-hoc model. Our results suggest that foraging songbirds only use social cues about the location of potential food sources, but not their profitability. These findings agree with the hypothesis that individuals balance the relative economic costs of using different information, where the costs of personally sampling a patch upon arrival is low relative to the cost of searching for patches. This study extends previous work on information spread through avian social networks, by suggesting important links between how animals use information at different stages of the acquisition process and the emerging population-level patterns of patch use.
Long-read Data Revealed Structural Diversity in Human Centromere Sequences
Authors: Suzuki Yuta , Myers Gene , Morishita Shinichi
Published: September 2019

Centromeres invariably serve as the loci of kinetochore assembly in all eukaryotic cells, but their underlying DNA sequences evolve rapidly. Human centromeres are characterized by their extremely repetitive structures, i.e., higher-order repeats, rendering the region one of the most difficult parts of the genome to assess. Consequently, our understanding of centromere sequence variations across human populations is limited. Here, we analyzed chromosomes 11, 17, and X using long sequencing reads of two European and two Asian genomes, and our results show that human centromere sequences exhibit substantial structural diversity, harboring many novel variant higher-order repeats specific to individuals, while frequent single-nucleotide variants are largely conserved. Our findings add another dimension to our knowledge of centromeres, challenging the notion of stable human centromeres. The discovery of such diversity prompts further deep sequencing of human populations to understand the true nature of sequence evolution in human centromeres.
Single-cell genomics of uncultured bacteria reveals dietary fiber responders in the mouse gut microbiota
Authors: Chijiiwa Rieka , Hosokawa Masahito , Kogawa Masato , Nishikawa Yohei , Ide Keigo , Sakanashi Chikako , Takahashi Kai , Takeyama Haruko
Published: September 2019

Background

The gut microbiota can have dramatic effects on host metabolism; however, current genomic strategies for uncultured bacteria have several limitations that hinder their ability to identify responders to metabolic changes in the microbiota. In this study, we describe a novel single-cell genomic sequencing technique that can identify metabolic responders at the species level without the need for reference genomes, and apply this method to identify bacterial responders to an inulin-based diet in the mouse gut microbiota.

Results

Inulin feeding changed the mouse fecal microbiome composition to increase Bacteroides spp., resulting in the production of abundant succinate in the mouse intestine. Using our massively parallel single-cell genome sequencing technique, named SAG-gel platform, we obtained 346 single-amplified genomes (SAGs) from mouse gut microbes before and after dietary inulin supplementation. After quality control, the SAGs were classified as 267 bacteria, spanning two phyla, four classes, seven orders, and 14 families, and 31 different strains of SAGs were graded as high- and medium-quality draft genomes. From these, we have successfully obtained the genomes of the dominant inulin-responders, Bacteroides spp., and identified their polysaccharide utilization loci and their specific metabolic pathways for succinate production.

Conclusions

Our single-cell genomics approach generated a massive amount of SAGs, enabling a functional analysis of uncultured bacteria in the intestinal microbiome. This enabled us to estimate metabolic lineages involved in the bacterial fermentation of dietary fiber and metabolic outcomes such as short-chain fatty acid production in the intestinal environment based on the fibers ingested. The technique allows the in-depth isolation and characterization of uncultured bacteria with specific functions in the microbiota and could be exploited to improve human and animal health.
Rhythmic variations in prefrontal inter-neuronal correlations, their underlying mechanisms and their behavioral correlates
Authors: Ben Hadj Hassen S. , Gaillard C. , Astrand E. , Wardak C. , Ben Hamed S.
Published: September 2019

Functional neuronal correlations between pairs of neurons are thought to play an important role in neuronal information processing and optimal neuronal computations during attention, perception, decision-making and learning. These noise correlations are often assumed to be stable in time. However, recent studies suggest that cognitive processes are rhythmic, this rhythmicity accounting for variations in overt behavioral performance. Whether this rhythmicity coincides with variations in shared noise variability is unknown. Here, we perform simultaneous recordings from the macaque frontal eye fields, while animals are engaged in a spatial memory task. We report that noise correlations in prefrontal cortex fluctuate rhythmically in the high alpha (10-16Hz) and beta (20-30Hz) frequency ranges. Importantly, these rhythmic modulations in shared neuronal variability account for dynamic changes in overt behavioral performance. They also coincide with increased spike-LFP phase coupling in these specific frequency ranges, the spatial profile of which vary between superficial and deep cortical layers. Finally, we demonstrate, using an artificial neuronal model, that rhythmic variations in noise correlation oscillations parsimoniously arise from long range (LFP) and local spike-LFP phase coupling mechanisms. Thus a significant portion of noise correlation fluctuations can be attributed to long-range global network rhythmicity.
SPF45/RBM17-dependent, but not U2AF-dependent, splicing in a distinct subset of human short introns
Authors: Fukumura Kazuhiro , Yoshimoto Rei , Sperotto Luca , Kang Hyun-Seo , Hirose Tetsuro , Inoue Kunio , Sattler Michael , Mayeda Akila
Published: September 2019

Human pre-mRNA introns vary in size from under fifty to over a million nucleotides. We searched for essential factors involved in the splicing of human short introns by screening siRNAs against 154 human nuclear proteins. The splicing activity was assayed with a model HNRNPH1 pre-mRNA containing short 56-nucleotide intron. We identified a known alternative splicing regulator SPF45 (RBM17) as a constitutive splicing factor that is required to splice out this 56-nt intron. Whole-transcriptome sequencing of SPF45-deficient cells revealed that SPF45 is essential in the efficient splicing of many short introns. To initiate the spliceosome assembly on a short intron with the truncated poly-pyrimidine tract, the U2AF-homology motif (UHM) of SPF45 competes out that of U2AF65 for binding to the UHM-ligand motif (ULM) of the U2 snRNP protein SF3b155 (SF3B1). We propose that splicing in a distinct subset of human short introns depends on SPF45 but not U2AF heterodimer.
Design and Optimization Protocol for High-Dimensional Immunophenotyping Assays using Spectral Flow Cytometry
Authors: Ferrer-Font L , Pellefigues C , Mayer JU , Small S , Jaimes MC , Price KM
Published: September 2019

Technological advances in fluorescence flow cytometry and an ever-expanding understanding of the complexity of the immune system has led to the development of large 20+ flow cytometry panels. Yet, as panel complexity and size increases, so does the difficulty involved in designing a high-quality panel, accessing the instrumentation capable of accommodating large numbers of parameters, and in analysing such high-dimensional data.

A recent advancement is spectral flow cytometry, which in contrast to conventional flow cytometry distinguishes the full emission spectrum of each fluorochrome across all lasers, rather than identifying only the peak of emission. Fluorochromes with a similar emission maximum but distinct off-peak signatures can therefore be accommodated within the same flow cytometry panel, allowing greater flexibility in terms of panel design and fluorophore detection.

Here, we highlight the specific characteristics regarding spectral flow cytometry and aim to guide users through the process of building, designing and optimising high-dimensional spectral flow cytometry panels using a comprehensive step-by-step protocol. Special considerations are also given for using highly-overlapping dyes and a logical selection process an optimal marker-fluorophore assignment is provided.
Responses of global waterbird populations to climate change vary with latitude
Authors: Amano Tatsuya , Székely Tamás , Wauchope Hannah S. , Sandel Brody , Nagy Szabolcs , Mundkur Taej , Langendoen Tom , Blanco Daniel , Michel Nicole L. , Sutherland William J.
Published: September 2019

While climate change continues to present a major threat to global biodiversity and ecosystems, most research on climate change impacts do not have the resolution to detect changes in species abundance and are often limited to temperate ecosystems. This limits our understanding of global responses in species abundance—a determinant of ecosystem function and services—to climate change including in the highly-biodiverse tropics. We address this knowledge gap by quantifying abundance responses to climate change in waterbirds, an indicator taxon of wetland biodiversity, at 6,822 sites between −55° and 64°. Using 1,303,651 count records since 1990 of 390 species, we show that with temperature increase, the abundance of species and populations decreased at lower latitudes, particularly in the tropics, but increased at higher latitudes. These contrasting responses to temperature increase according to latitude indicate potential global-scale poleward shifts of species abundance under climate change, providing empirical support for predictions by earlier studies. The negative responses to temperature increase in tropical species and populations are of conservation concern, as they are often also threatened by other anthropogenic factors. Our results suggest that existing biases in studies towards temperate regions could underestimate the impact of climate change on waterbirds and other species.
Positive relation between arcuate fasciculus white matter fiber structure and severity of auditory hallucinations: A DTI tractography study
Authors: Falkenberg Liv E. , Westerhausen René , Johnsen Erik , Kroken Rune , Løberg Else-Marie , Beresniewicz Justyna , Kazimierczak Katarzyna , Kompus Kristiina , Ersland Lars , Hugdahl Kenneth
Published: September 2019

The arcuate fasciculus (AF) has been implicated in the pathology behind schizophrenia and auditory verbal hallucinations (AVHs). White matter tracts forming the arcuate fasciculus can be quantified and visualized using diffusion tensor imaging (DTI) tractography. Although there have been a number of studies on this topic, the results have been conflicting. Studying the underlying white matter structure of the AF could shed light on functional connectivity between temporal and frontal language areas in AVHs. The participants were 66 patients with a schizophrenia diagnosis, where AVHs were defined from the Positive and Negative Syndrome Scale (PANSS), and compared with a healthy control group. DTI was performed on a 3T MR scanner, and tensor estimation was done using deterministic streamline tractography. Statistical analysis of the data showed significantly longer tracts along the AF in patients with severe and frequent AVHs, as well as an overall significant asymmetry with longer fibers on the left side. In addition, there were significant positive correlations between PANSS scores and tract length, tract volume, and number of streamlines for the posterior AF segment on the left side. It is concluded that the present structural results complement previous functional findings of fronto-temporal connectivity in AVH patients.
The Brazilian Amazon Protected Area Network was largely unaffected by recent satellite-detectable fires
Authors: Bebber Daniel P.
Published: September 2019

August 2019 saw dramatic increases in wildfires in the Brazilian Amazon, leading to arguments between Brazil and G7 leaders and widespread concern among conservationists. Popular media reports suggested that ‘swathes of the Amazon rainforest in Brazil are on fire’. Here we investigate the spatial distribution of fires through August 2019, showing that fires were largely restricted to deforested regions and areas with low canopy cover, particularly in unprotected areas that comprise half the region. In contrast, Brazil’s protected areas had one third as many fires, and forest in protected areas with high canopy cover was almost entirely unaffected by fire. Protected areas reduce deforestation and carbon emissions, and have proved largely untouched by recent fires. However, fires in closed-canopy forest cannot readily be detected by satellite remote-sensing and so this analysis likely underestimates the burned area in intact forest, both in protected and unprotected areas.
A quantitative binding model for the Apl protein, the dual purpose recombination-directionality factor and lysis-lysogeny regulator of bacteriophage 186
Authors: Cutts Erin , Egan J. Barry , Dodd Ian , Shearwin Keith
Published: September 2019

The Apl protein of bacteriophage 186 functions both as an excisionase and as a transcriptional regulator; binding to the phage attachment site (att), and also between the major early phage promoters (pR-pL). Like other recombination directionality factors (RDFs), Apl binding sites are direct repeats spaced one DNA helix turn apart. Here, we use in vitro binding studies with purified Apl and pR-pL DNA to show that Apl binds to multiple sites with high cooperativity, bends the DNA, and spreads from specific binding sites into adjacent non-specific DNA; features that are shared with other RDFs. By analysing Apl’s repression of pR and pL, and the effect of operator mutants in vivo with a simple mathematical model, we were able to extract estimates of binding energies for single specific and non-specific sites and for Apl cooperativity, revealing that Apl monomers bind to DNA with low sequence specificity but with strong cooperativity between immediate neighbours. This model fit was then independently validated with in vitro data. The model we employed here is a simple but powerful tool that enabled better understanding of the balance between binding affinity and cooperativity required for RDF function. A modelling approach such as this is broadly applicable to other systems.
Checklist and practical identification key for the cichlid fishes (Cichliformes: Cichlidae) of the La Plata drainage in Bolivia, including three new geographical records
Authors: Hablützel Pascal I. , Huanto Robert B.
Published: September 2019

In comparison with the Bolivian Amazon, the ichthyofauna of the La Plata drainage of Bolivia received relatively little attention historically. Until now, 14 species of cichlid fish have been registered from this area. After an exhaustive review of museum collections (Museo de Historia Natural Noel Kempff Mercado y Colección Boliviana de Fauna), we can report three additional species:Astronotus crassipinnis(Heckel, 1840),Mesonauta festivus(Heckel, 1840) andSatanoperca pappaterra(Heckel, 1840). Four other species, which have been listed in previous publications, can be confirmed for the La Plata drainage of Bolivia based on the examination of voucher specimens:Aequidens plagiozonatusKullander, 1984,Apistogramma commbrae(Regan, 1906),A. trifasciata(Eigenmann & Kennedy, 1903) andCrenicichla vittataHeckel, 1840. As such, 16 of the 17 species can be referenced with voucher specimens in museum collections. We also provide an identification key for the cichlid fish species of the study area.
Systemic muscle wasting and coordinated tumour response drive tumourigenesis
Authors: Newton Holly , Wang Yi-Fang , Camplese Laura , Brown André E.X. , Hirabayashi Susumu
Published: September 2019

Cancer cells demand excess nutrients to support their proliferation, but how tumours exploit extracellular amino acids during systemic metabolic pertubations remain incompletely understood. Here we use a Drosophila model of obesity-enhanced tumourigenesis to uncover a systemic host-tumour nutrient circuit that supports tumour growth. We demonstrate coordinate induction of systemic cachexia-like muscle wasting with tumour-autonomous SLC36-family amino acid transporter expression as a proline-scavenging programme to drive tumourigenesis. This coordinated induction of cachexia and SLC36-transporters pertains to human kidney cancer and associates with significantly worse survival outcomes. We identify Indole-3-propionic acid as an optimal amino acid derivative to rationally target the proline-dependency of tumour growth. Combining insights from whole-animal Drosophila models and human cancer database analysis provides a powerful approach towards the identification and therapeutic exploitation of the amino acid vulnerabilities of tumourigenesis in the context of perturbed systemic metabolic network.
Maternal hypothyroidism in mice influences glucose metabolism in adult offspring
Authors: Kemkem Yasmine , Nasteska Daniela , De Bray Anne , Bargi-Souza Paula , Peliciari-Garcia Rodrigo A. , Guillou Anne , Mollard Patrice , Hodson David J. , Schaeffer Marie
Published: September 2019

During pregnancy, maternal metabolic diseases and hormonal imbalance may alter fetal beta cell development and/or proliferation, thus leading to an increased risk for developing type 2 diabetes in adulthood. Although thyroid hormones play an important role in fetal endocrine pancreas development, the impact of maternal hypothyroidism on glucose homeostasis in adult offsprings remains poorly understood. Here, we show that when fed normal chow, adult mice born to hypothyroid mothers were more glucose-tolerant due to beta cell hyperproliferation and increased insulin sensitivity. However, following high fat feeding, these offsprings became profoundly hyperinsulinemic, insulin-resistant and glucose-intolerant compared to controls from euthyroid mothers. Suggesting presence of epigenetic changes, altered glucose metabolism was maintained in a second generation of animals. As such, gestational hypothyroidism induces long-term and persistent alterations in endocrine pancreas function, which may have important implications for type 2 diabetes prevention in affected individuals.

SIGNIFICANCE

Diabetes and hypothyroidism are two major public health issues, affecting ∼ 9 and 2 % of the population worldwide, respectively. As master metabolic gatekeepers, the thyroid hormones play an essential role in metabolism and fetal development. However, gestation increases demand on the thyroid axis in the mother, leading to hypothyroidism in 0.5 % of pregnancies. Maternal hypothyroidism is associated with deficits in fetal growth that may lead to long-term alterations in metabolism in the offspring. We therefore sought to investigate the effects of gestational hypothyroidism on glucose metabolism in adult offspring and their descendants, and how this may predispose to diabetes development.
Dissecting the structural and functional roles of a vicinal iron-binding site in encapsulated ferritins
Authors: Piergentili Cecilia , Ross Jennifer , He Didi , Gallagher Kelly J. , Stanley Will A. , Adam Laurène , Mackay C. Logan , Waldron Kevin J. , Clarke David J. , Marles-Wright Jon
Published: September 2019

Encapsulated ferritins belong to the universally distributed ferritin superfamily, which function as iron detoxification and storage systems. Encapsulated ferritins have a distinct annular structure and must associate with an encapsulin nanocage to form a competent iron store that is capable of holding significantly more iron than classical ferritins. The catalytic mechanism of iron oxidation in the ferritin family is still an open question, due to differences in organization of the ferroxidase catalytic site and secondary metal binding sites vicinal to this. We have previously identified a metal binding site on the inner surface of theRhodospirillum rubrumencapsulated ferritin at the interface between the two-helix subunits and proximal to the ferroxidase center. Here we present a comprehensive structural and functional study to investigate the functional relevance of this proposed iron entry site by means of enzymatic assays, mass-spectrometry, and X-ray crystallography. We show that catalysis occurs in the ferroxidase center and suggest a dual role for the secondary site, which both serves to attract metal ions to the ferroxidase center and acts as a flow-restricting valve to limit the activity of the ferroxidase center. Moreover, confinement of encapsulated ferritins within the encapsulin nanocage, while enhancing the ability of the encapsulated ferritin to undergo catalysis, does not influence the function of the secondary site.
Monodelphis domesticaas a fetal intra-cerebral inoculation model for Zika virus pathogenesis
Authors: Thomas John M. , Garcia Juan , Terry Matthew , Lozano Ileana , Mahaney Susan M. , Quintanilla Oscar , Carlo-Silva Dionn , Morales Marisol , VandeBerg John L.
Published: September 2019

Monodelphis domestica, also known as the laboratory opossum, is a marsupial native to South America. At birth, these animals are developmentally equivalent to human embryos at approximately 5 weeks of gestation which, when coupled with other characteristics including the size of the animals, the development of a robust immune system during juvenile development, and the relative ease of experimental manipulation, have madeM. domesticaa valuable model in many areas of biomedical research. However, their suitability as models for infectious diseases, especially diseases caused by viruses such as Zika virus (ZIKV), is currently unknown. Here, we describe the replicative effects of ZIKV using a fetal intra-cerebral model of inoculation. Using immunohistochemistry and in situ hybridization, we found that opossum embryos and fetuses are susceptible to infection by ZIKV administered intra-cerebrally, that the infection persists long term, and that the infection and viral replication consistently results in neural pathology and may occasionally result in global growth restriction. These results demonstrate the utility ofM. domesticaas a new animal model for investigating ZIKV infectionin vivo.This new model will facilitate further inquiry into viral pathogenesis, particularly for those viruses that are neurotropic, that may require a host with the ability to support sustained viral infection, and/or that may require intra-cerebral inoculations of large numbers of embryos or fetuses.

AUTHOR SUMMARY

Here we show that the laboratory opossum (Monodelphis domestica) is a valuable new model for studying Zika virus pathogenesis. Newborns are at the developmental stage of 5-week human embryos. Zika virus inoculated on a single occasion into the brains of pups at the human developmental stages of 8-20 weeks post conception replicated in neuronal cells and persisted as a chronic infection until the experimental endpoint at 74-days post infection. In addition, we observed global growth restriction in one of 16 inoculated animals; global growth restriction has been observed in humans and other animal models infected with Zika virus. The results illustrate great potential for this new animal model for high throughput research on the neurological effects of Zika virus infection of embryos and fetuses.
The fast and the frugal: Divergent locomotory strategies drive limb lengthening in theropod dinosaurs
Authors: Dececchi T. Alexander , Mloszewska Aleksandra M. , Holtz Thomas R. , Habib Michael B. , Larsson Hans C.E.
Published: September 2019

Limb length, cursoriality and speed have long been areas of significant interest in theropod paleobiology as locomotory capacity, especially running ability, is critical in not just in prey pursuit but also to avoid become prey oneself. One aspect that is traditionally overlooked is the impact of allometry on running ability and the limiting effect of large body size. Since several different non-avian theropod lineages have each independently evolved body sizes greater than any known terrestrial carnivorous mammal, ∼1000kg or more, the effect that such larger mass has on movement ability and energetics is an area with significant implications for Mesozoic paleoecology. Here using expansive datasets, incorporating several different metrics to estimate body size, limb length and running speed, to calculate the effects of allometry running We test both on traditional metrics used to evaluate cursoriality in non-avian theropods such as distal limb length, relative hindlimb length as well as comparing the energetic cost savings of relative hindlimb elongation between members of the Tyrannosauridae and more basal megacarnivores such as Allosauroids or Ceratosauridae. We find that once the limiting effects of body size increase is incorporated, no commonly used metric including the newly suggested distal limb index (Tibia + Metatarsus/ Femur length) shows a significant correlation to top speed. The data also shows a significant split between large and small bodied theropods in terms of maximizing running potential suggesting two distinct strategies for promoting limb elongation based on the organisms’ size. For small and medium sized theropods increased leg length seems to correlate with a desire to increase top speed while amongst larger taxa it corresponds more closely to energetic efficiency and reducing foraging costs. We also find, using 3D volumetric mass estimates, that the Tyrannosauridae show significant cost of transport savings compared to more basal clades, indicating reduced energy expenditures during foraging and likely reduced need for hunting forays. This suggests that amongst theropods while no one strategy dictated hindlimb evolution. Amongst smaller bodied taxa the competing pressures of being both a predator and a prey item dominant while larger ones, freed from predation pressure, seek to maximize foraging ability. We also discuss the implications both for interactions amongst specific clades and Mesozoic paleobiology and paleoecological reconstructions as a whole.
Evolution from total variation to nonlinear sparsifying transform for sparse-view CT image reconstruction
Authors: Dong Jian , Han Chunxiao , Qin Zhuanping , Che Yanqiu
Published: September 2019

Sparse-view CT has been widely studied as an effective strategy for reducing radiation dose to patients. However, the conventional image reconstruction algorithms, such as filtered back-projection method and classical algebraic reconstruction techniques, can no longer be competent in the image reconstruction task of sparse-view CT. A new principle, called compressed sensing (CS), has been therefore developed to provide an effective solution for the ill-posed inverse problem of sparse-view CT image reconstruction. Total variation (TV) minimization, which is most extensively studied among the existing CS techniques, has been recognized as a powerful tool for dealing with this difficult problem in image reconstruction community. However, in recent years, the drawbacks of TV are being increasingly reported, which are appearance of patchy artifacts, depict of incorrect object boundaries, and loss in image textures or smooth intensity changes. These degradations appear especially in reconstructing actual CT images with complicated intensity changes. In order to address these drawbacks, a series of advanced algorithms using nonlinear sparsifying transform (NLST) have been proposed very recently. The NLST-based CS is based on a different framework from the TV, and it achieves an improvement in image quality. Since it is a relatively newly proposed idea, within the scope of our knowledge, there exist few literatures that discusses comprehensively how the image quality improvement occurs in comparison with the conventional TV method. In this study, we investigated the image quality differences between the conventional TV minimization and the NLST-based CS, as well as image quality differences among different kinds of NLST-based CS algorithms in the sparse-view CT image reconstruction. More specifically, image reconstructions of actual CT images of different body parts were carried out to demonstrate the image quality differences.