bluuebunny/crossref_metadata_2025_split huggingface dataset:
A binocular perception deficit characterizes prey pursuit in developing mice
Authors: Allen Kelsey , Gonzalez-Olvera Rocio , Kumar Milen , Feng Ting , Pieraut Simon , Hoy Jennifer L. 
Published: May 2022

AbstractThe mouse continues to be one of the most powerful models in which to address the molecular and cellular mechanisms underlying mammalian visual system development. In particular, integration of binocular information at the cellular level has long been studied in specific regions of the mouse visual cortex to gain mechanistic insight into the development of vision. However, we lack an understanding of the development of the visual perceptions themselves in mice and other species that might rely on successful binocular integration. Further, the superior colliculus also processes binocular input and it remains unclear how early visual experience differentially impacts activity in this brain area during behavior. To address these major outstanding questions, we quantified the natural visually-guided behavior of postnatal day 21 (P21) and adult mice using a live prey capture assay and a computerized-spontaneous perception of visual objects tasks (C-SPOT). Analysis of both behavioral assays revealed robust and specific binocular visual field processing deficits in P21 mice as compared to adults. In addition, c-Fos expression in the anterior region of the superior colliculus (SC), the region that would process stimuli located in the binocular visual field, was highly different between P21 mice and adults after C-SPOT. We thus exploited a natural visual pursuit behavior and C-SPOT to provide the first demonstration of a specific visual perception deficit related to binocular integration in developing mice.HighlightsJuvenile (P21) mice robustly investigate live insectsInsect pursuit behavior relying on binocular vision is immature in P21 miceVisually-induced arrest responses are similar between P21 and adult mice.Ethologically-relevant visual experience differentially increases c-Fos expression in the superior colliculus of juveniles versus adults.
Distinct types of multicellular aggregates in Pseudomonas aeruginosa liquid cultures
Authors: Melaugh Gavin , Martinez Vincent , Baker Perrin , Hill Preston , Howell P. Lynne , Wozniak Daniel J. , Allen Rosalind J. 
Published: May 2022

ABSTRACTPseudomonas aeruginosa forms suspended multicellular aggregates when cultured in liquid media. Such aggregates may be important in disease, and/or as a pathway to biofilm formation. The polysaccharide Psl and extracellular DNA (eDNA) have both been implicated in aggregation, but previous results depend strongly on the experimental conditions. Here we develop a quantitative microscopy-based method for assessing changes in the size distribution of suspended aggregates over time in growing cultures. For exponentially growing cultures of P. aeruginosa PAO1, we find that aggregation is mediated by cell-associated Psl, rather than by either eDNA or se-creted Psl. These aggregates arise de novo within the culture via a growth process that involves both collisions and clonal growth. They are “non-cheatable” since Psl non-producing cells do not aggregate with producers. In contrast, we find that stationary phase (overnight) cultures contain a different type of multicelullar aggregate, in which both eDNA and Psl mediate cohesion. Our findings suggest that the physical and bi-ological properties of multicellular aggregates may be very different in early-stage vs late-stage bacterial cultures.
Museum specimens of a landlocked pinniped reveal recent loss of genetic diversity and unexpected population connections
Authors: Heino Matti T. , Nyman Tommi , Palo Jukka U. , Harmoinen Jenni , Valtonen Mia , Pilot Małgorzata , Översti Sanni , Salmela Elina , Kunnasranta Mervi , Hoelzel A. Rus , Ruokonen Minna , Aspi Jouni 
Published: May 2022

AbstractAimThe Saimaa ringed seal (Pusa hispida saimensis) is endemic to Lake Saimaa in Finland. The subspecies is thought to have originated when parts of the ringed seal population of the Baltic region were trapped in lakes emerging due to post-glacial bedrock rebound around 9,000 years ago. During the 20th century, the population experienced a drastic human-induced bottleneck. Today encompassing a little over 400 seals with extremely low genetic diversity, it is classified as endangered. Our main aim was to evaluate the role of the 20th century bottleneck in the erosion of genetic diversity in the Saimaa seal population. We also evaluated connections with other ringed seals from the Baltic Sea, Lake Ladoga, North America, Svalbard and the White Sea.LocationLake Saimaa, Finland, together with the Baltic Sea and the Arctic Ocean.MethodsWe sequenced sections of the mitochondrial control region from 60 up to 125 years old museum specimens of the Saimaa ringed seal. The generated dataset was combined with publicly available sequences. We studied how genetic variation has changed through time in this subspecies, and how it is phylogenetically related to other ringed seal populations.ResultsWe observed temporal fluctuations in haplotype frequencies and loss of haplotypes accompanied by a recent reduction in female effective population size. In apparent contrast with the traditionally held view of the Baltic origin of the population, the Saimaa ringed seal mtDNA variation shows also affinities to North American ringed seals.Main conclusionsOur results suggest that the Saimaa ringed seal has experienced recent genetic drift associated with small population size. The results further suggest that extant Baltic ringed seals do not represent well the ancestral population of the Saimaa ringed seal, which calls for re-evaluation of the deep history of this subspecies.
In-situ lipid profiling of insect pheromone glands by Direct Analysis in Real Time Mass Spectrometry
Authors: Cetraro Nicolas , Yew Joanne Y. 
Published: May 2022

AbstractLipid pheromones play a significant role in the behavior and ecology of many insects. The characterization of pheromone structures is a significant challenge due to their low abundance and ephemeral nature. Here we present a method for the analysis of lipid molecules from single pheromone glands of Drosophila melanogaster (fruit fly) using Direct Analysis in Real Time mass spectrometry (DART MS). Our results reveal that DART MS analysis of single tissues generates reproducible, species-specific lipid profiles comprised of fatty acids, wax esters, diacylglycerides and triacylglycerides. In addition, the ion source temperature and application of a solvent wash can cause significant qualitative and quantitative changes in the mass spectral profile. Lastly, we show that untargeted chemical fingerprinting of the gland can be used to accurately categorize species according to phylogenetic subgroup or genotype. Collectively, our findings indicate that DART MS is a rapid and powerful method for characterizing a broad range of lipids in tissues with minimal preparation. The application of direct tissue DART MS will expand the “secretome” of molecules produced by pheromone glands. In addition to its direct relevance to chemical ecology, the method could potentially be used in pharmaceutical studies for the screening and detection of tissue-specific drug metabolites.
Basic Leucine Zippers: Aureochromes Versus the Rest
Authors: Khamaru Madhurima , Deb Anwesha , Mitra Devrani 
Published: May 2022

AbstractThe photoreceptor cum transcription factors, Aureochromes, is present exclusively in marine photosynthetic algae. Co-existence of Light-Oxygen-Voltage (LOV) sensor and basic leucine zipper (bZIP) effector in aureochromes is unique -- no other photoreceptors barring aureochromes are known to possess bZIP as effector. The ability of aureochromes to participate in diverse biological activities, inverse topological arrangement make them a model protein not only to study light-dependent gene expression or transcriptional regulation but also as potential optogenetic scaffold. While detailed structural information is available for the LOV sensor, 3D structural information is absent for bZIP/bZIP+linker+LOV module. This study therefore aims for a thorough investigation of the bZIP domains from aureochromes and others, and their interaction with substrate DNA using tools from sequence/structural bioinformatics and network theory. With an in-depth comparison between 26 aureochrome subtypes and 147 plant/ophistokont bZIPs, we explore important residues at basic region and zipper - necessary for dimerization stability and DNA binding specificity. Perhaps the most notable finding is the unique histidine substitution at the DNA binding signature sequence of aureochromes, completely absent in any other bZIPs. Not only is this residue important for DNA binding, this can serve as a potential switch point in aureochrome/bZIP evolution. An all-atom network analysis on representative bZIP-DNA co-crystal structures, especially the measurement of eigenvector centrality, further adds importance to hydrophobic interactions in the zipper region to stabilize bZIP dimer and facilitate DNA binding.
A type IV Autotaxin inhibitor ameliorates acute liver injury and non-alcoholic steatohepatitis in mice
Authors: Booijink Richell , Salgado-Polo Fernando , Jamieson Craig , Perrakis Anastassis , Bansal Ruchi 
Published: May 2022

AbstractAn important but rather underexplored pathway implicated in liver disease is the lysophosphatidic acid (LPA) signaling axis. LPA acts through G-protein coupled receptors inducing downstream signaling pathways related to cell proliferation, differentiation, and migration, and is predominantly produced by the extracellular phosphodiesterase, Autotaxin (ATX). ATX has gained significant attention lately with an impressive number of ATX inhibitors (type I-IV) reported. Here, we aim to evaluate the therapeutic potential of a (yet unexplored) type IV ATX inhibitor, Cpd17, in liver injury. In this study, we first confirmed the involvement of the ATX/LPA signaling axis in human and murine diseased livers. Thereafter, we evaluated the effects of Cpd17, in comparison with the classic type I ATX inhibitor PF8380, in vitro. While both inhibitors attenuated induced cell injury phenotypes as assessed using various assays and specific readout parameters in hepatocytes, macrophages, and hepatic stellate cells (HSCs), Cpd17 appeared more effective. This prompted us to characterize the mechanism of action of both inhibitors in situ and in vitro in macrophages and HSCs, demonstrating that Cpd17 was more potent in inhibiting relevant signaling pathways, namely RhoA-mediated cytoskeletal remodeling, and phosphorylation of MAPK/ERK and AKT/PKB. Finally, we investigated the therapeutic potential of Cpd17 in two liver disease mouse models, CCl4-induced acute liver injury and diet-induced non-alcoholic steatohepatitis. We demonstrate that Cpd17 has an excellent potential for reducing liver injury in both disease models in vivo. We conclude that ATX inhibition, by type IV inhibitor in particular, has an excellent potential for clinical application in liver diseases.
Membrane Bound O-Acyltransferase 7 (MBOAT7)-Driven Lysophosphatidylinositol (LPI) Acylation in Adipocytes Contributes to Systemic Glucose Homeostasis
Authors: Massey William , Varadharajan Venkateshwari , Banerjee Rakhee , Brown Amanda L. , Horak Anthony J. , Hohe Rachel C. , Chan E. Ricky , Pan Calvin , Zhang Renliang , Allende Daniela S. , Lusis Aldons J. , Brown J. Mark 
Published: May 2022

AbstractNon-alcoholic fatty liver disease (NAFLD) is becoming increasingly common and is a leading cause of end stage liver diseases such as cirrhosis and hepatocellular carcinoma. The rise in NAFLD closely parallels the global epidemic of obesity and type 2 diabetes mellitus (T2DM), and there is a clear interrelationship between abnormal lipid metabolism, insulin resistance, and NAFLD progression. Several genetic loci have been identified as contributors to NAFLD progression, all of which are consistently linked to abnormal lipid metabolic processes in the liver. The common loss-of-function variant rs641738 (C>T) near the gene encoding Membrane-Bound O-Acyltransferase 7 (MBOAT7) is associated with increased susceptibility to NAFLD as well as the entire spectrum of NAFLD progression. The MBOAT7 gene encodes a lipid metabolic enzyme that is capable of esterifying polyunsaturated fatty acyl-CoAs to LPI substrates to generate phosphatidylinositol (PI) lipids. We previously showed that antisense oligonucleotide (ASO)-mediated knockdown of Mboat7 in mice promoted high fat diet-induced hepatic steatosis, hyperinsulinemia, and systemic insulin resistance (Helsley et al., 2019). Thereafter, other groups showed that hepatocyte-specific genetic deletion of Mboat7 promoted striking fatty liver and NAFLD progression but does not alter insulin sensitivity, suggesting the potential for cell autonomous roles. Here, we show that MBOAT7 function in adipocytes contributes to diet-induced metabolic disturbances including hyperinsulinemia and systemic insulin resistance. The expression of Mboat7 in white adipose tissue closely correlates with diet-induced obesity across a panel of ∼100 inbred strains of mice fed a high fat/high sucrose diet. Moreover, adipocyte-specific genetic deletion of Mboat7 is sufficient to promote hyperinsulinemia, systemic insulin resistance, and mild fatty liver. Unlike in the liver, where Mboat7 plays a relatively minor role in maintaining arachidonic acid (AA)-containing PI pools, Mboat7 is the major source of AA-containing PI pools in adipose tissue. Our data demonstrate that MBOAT7 is a critical regulator of adipose tissue PI homeostasis, and adipocyte MBOAT7-driven PI biosynthesis is closely linked to hyperinsulinemia and insulin resistance in mice.
QTL mapping for seed morphology using the instance segmentation neural network inLactucaspp
Authors: Seki Kousuke , Toda Yosuke 
Published: May 2022

AbstractWild species of lettuce (Lactucasp.) are thought to have first been domesticated for oilseed contents to provide seed oil for human consumption. Although seed morphology is an important trait contributing to oilseed in lettuce, the underlying genetic mechanisms remain elusive. Since lettuce seeds are small, a manual phenotypic determination required for a genetic dissection of such traits is challenging. In this study, we built and applied an instance segmentation-based seed morphology quantification pipeline to measure traits in seeds generated from a cross between the domesticated oilseed type cultivar ‘Oilseed’ and the wild species ‘UenoyamaMaruba’ in an automated manner. Quantitative trait locus (QTL) mapping following ddRAD-seq revealed 11 QTLs linked to 7 seed traits (area, width, length, length-to-width ratio, eccentricity, perimeter length, and circularity). Remarkably, the three QTLs with the highest LOD scores,qLWR-3.1, qECC-3.1, andqCIR-3.1, for length-to-width ratio, eccentricity, and circularity, respectively, mapped to linkage group 3 (LG3) around 161.5 to 214.6 Mb, a region previously reported to be associated with domestication traits from wild species. These results suggest that the oilseed cultivar harbors genes acquired during domestication to control seed shape in this genomic region. This study also provides genetic evidence that domestication arose, at least in part, by selection for the oilseed type from wild species and demonstrates the effectiveness of image-based phenotyping to accelerate discoveries of the genetic basis for small morphological features such as seed size and shape.
Expanded Distribution and Predicted Suitable Habitat for the Critically Endangered Yellow-tailed Woolly Monkey (Lagothrix flavicauda) in Peru
Authors: Zarate Melissa A. , Shanee Sam , Charpentier Elvis , Sarmiento Yeissy , Schmitt Christopher A. 
Published: May 2022

ABSTRACTThe Tropical Andes Biodiversity Hotspot holds a remarkable number of species at risk of extinction due to anthropogenic habitat loss, hunting and climate change. One of these species, the Critically Endangered yellow-tailed woolly monkey (Lagothrix flavicauda), was recently sighted in Junín region, 206 kilometres south of its previously known distribution. The range extension, combined with continued habitat loss, calls for a re-evaluation of the species’ distribution and available suitable habitat. Here, we present novel data from surveys at 53 sites in the regions of Junín, Cerro de Pasco, Ayacucho and Cusco. We encounteredL. flavicaudaat 9 sites, all in Junín, and the congenericL. l. tschudiiat 20 sites, but never in sympatry. Using these new localities along with all previous geographic localities for the species, we made predictive Species Distribution Models based on Ecological Niche Modelling using a generalized linear model and maximum entropy. Each model incorporated bioclimatic variables, forest cover, vegetation measurements, and elevation as predictor variables. Model evaluation showed >80% accuracy for all measures. Precipitation was the strongest predictor of species presence. Habitat suitability maps illustrate potential corridors for gene flow between the southern and northern populations, although much of this area is inhabited byL. l. tschudii. An analysis of the current protected area (PA) network showed ∼47% of remaining suitable habitat is unprotected. With this, we suggest priority areas for new protected areas or expansions to existing reserves that would conserve potential corridors betweenL. flavicaudapopulations. Further surveys and characterization of the distribution in intermediate areas, combined with studies on genetic flow, are still needed to protect this species.
A comparison between Mini-loop mediated isothermal amplification and polymerase spiral reaction for selective amplification of short template DNA
Authors: Allsopp RC , Alexandrou G , Toumazou C , Ali S , Charles Coombes R , Kalofonou M , Shaw J A 
Published: May 2022

AbstractIsothermal amplification of circulating tumour-derived DNA (ctDNA) in the blood plasma could provide a rapid and cost effective alternative to PCR and NGS approaches for real-time cancer monitoring. Several variations of isothermal technologies exist, typically designed over unconstrained template length. Here, we compared the amplification efficiency of a compact loop mediated isothermal amplification reaction (termed AS-Mini-LAMP) with polymerase spiral reaction (PSR) suitable for analysis of ctDNA. Utilising 4-primers and targeting a 155 bp template encompassing the estrogen receptor (ESR1) c.1138G>C (p.E380Q) missense mutation.Using synthetic E380Q template DNA and Bst2.0 polymerase, results demonstrate that AS-Mini-LAMP was capable of selective mutant allele DNA amplification to a limit of 1,000 mutant copies, whereas no specific amplification was observed by PSR. The alternative use of Bst3.0 polymerase for either AS-Mini-LAMP or PSR revealed non-canonical events that underpin potentially misleading results when employing isothermal chemistries. In conclusion, AS-Mini-LAMP is more suited to mutation detection than PSR.
Host adaptation drives genetic diversity in a vector-borne disease system
Authors: Combs Matthew A. , Tufts Danielle M. , Adams Ben , Lin Yi-Pin , Kolokotronis Sergios-Orestis , Diuk-Wasser Maria A. 
Published: May 2022

AbstractThe range of hosts a pathogen can infect is a key trait influencing human disease risk and reservoir host infection dynamics. Borrelia burgdorferi sensu stricto (Bb), an emerging zoonotic pathogen, causes Lyme disease and is widely considered a host generalist, commonly infecting mammals and birds. Yet the extent of intraspecific variation in Bb host breadth, its role in determining host competence and potential implications to human infection remain unclear. We conducted a long-term study of Bb diversity, defined by the polymorphic ospC locus, across white-footed mice, passerine birds, and tick vectors leveraging long-read amplicon sequencing. Our results reveal strong variation in host breadth across Bb genotypes, exposing a spectrum of genotype-specific host-adapted phenotypes. We found support for multiple niche polymorphism maintaining Bb diversity in nature and little evidence of temporal shifts in genotype dominance, as would be expected under negative frequency-dependent selection. Passerine birds support the circulation of several human invasive strains in the local tick population and harbor greater Bb genotypic diversity compared to white-footed mice. Mouse-adapted Bb genotypes exhibited longer persistence in individual mice compared to non-adapted genotypes and infection communities infecting individual mice preferentially became dominated by mouse-adapted genotypes over time. We posit that intraspecific variation in Bb host breadth and specificity helps maintain overall species fitness in response to transmission by a generalist vector. Because pathogen genotypes vary in host breadth and result in diverse human disease manifestations, our findings indicate that a more nuanced definition of ‘host competence’ incorporating local genotype frequency is warranted.SignificanceLyme disease is the most common vector-borne disease in the US with a causative agent (Borrelia burgdorferi) exhibiting high genetic diversity that partially correlates with human disease manifestations. Understanding the extent of host specificity in pathogens is critical for evaluating disease risk, but host specificity and mechanisms maintaining genetic diversity in Bb are unknown. We show that Bb genotypes exhibit variable host adaptation to white-footed mice and passerine birds, two common reservoir hosts, which appears to promote high intraspecific pathogen diversity. Conversely, we find limited evidence of negative frequency-dependent selection, an alternative mechanism for diversity maintenance. Our results reveal cryptic intraspecies host breadth variation and suggest that evaluating host competence depends on the frequency of host-adapted genotypes in local environments.
Overexpression screen of chromosome 21 genes reveals modulators of Sonic hedgehog signaling relevant to Down syndrome
Authors: Moyer Anna J. , Fernandez Fabian-Xosé , Li Yicong , Klinedinst Donna K. , Florea Liliana D. , Kazuki Yasuhiro , Oshimura Mitsuo , Reeves Roger H. 
Published: May 2022

AbstractDysregulation of Sonic hedgehog (SHH) signaling may contribute to multiple Down syndrome-associated phenotypes, including cerebellar hypoplasia, congenital heart defects, craniofacial and skeletal dysmorphologies, and Hirschsprung disease. Granule cell precursors isolated from the developing cerebellum of Ts65Dn mice are less responsive to the mitogenic effects of SHH than euploid cells, and a single postnatal dose of the SHH pathway agonist SAG rescues cerebellar morphology and performance on learning and memory tasks in Ts65Dn mice. SAG treatment also normalizes expression levels of OLIG2 in neural progenitor cells derived from human trisomy 21 iPSCs. However, despite evidence that activating SHH signaling can ameliorate some Down syndrome-associated phenotypes, chromosome 21 does not encode any components of the canonical SHH pathway. Here, we screened 163 chromosome 21 cDNAs in a series of SHH-responsive cell lines to identify chromosome 21 genes that modulate SHH signaling. We confirmed overexpression of trisomic candidate genes using RNA-seq in Ts65Dn and TcMAC21 cerebellum. Our study indicates that some chromosome 21 genes, including DYRK1A, upregulate SHH signaling while others, such as HMGN1 and MIS18A, inhibit SHH signaling. Overexpression of genes involved in chromatin structure and mitosis, but not genes previously implicated in ciliogenesis, regulate the SHH pathway. Our data suggest that cerebellar hypoplasia and other phenotypes related to aberrant SHH signaling arise from the net effect of trisomy for multiple chromosome 21 genes rather than the overexpression of a single trisomic gene. Identifying which chromosome 21 genes modulate SHH signaling may suggest new therapeutic avenues for ameliorating Down syndrome phenotypes.One Sentence SummaryMultiple chromosome 21 genes modulate Sonic hedgehog signaling, which is dysregulated in Down syndrome.