bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural genomic variation leads to unexpected genetic differentiation in Lake Tanganyika’s sardines
Authors: Junker Julian , Rick Jessica A. , McIntyre Peter B. , Kimirei Ismael , Sweke Emmanuel A. , Mosille Julieth B. , Wehrli Bernhard , Dinkel Christian , Mwaiko Salome , Seehausen Ole , Wagner Catherine E. 
Published: October 2019

AbstractIdentifying patterns in genetic structure and the genetic basis of ecological adaptation is a core goal of evolutionary biology and can inform the management and conservation of species that are vulnerable to population declines exacerbated by climate change. We used reduced representation genomic sequencing methods to gain a better understanding of genetic structure among and within populations of Lake Tanganyika’s two sardine species,Limnothrissa miodonandStolothrissa tanganicae. Samples of these ecologically and economically important species were collected across the length of Lake Tanganyika, as well as from nearby Lake Kivu, whereL. miodonwas introduced in 1959. Our results reveal unexpected differentiation within bothS. tanganicaeandL. miodonthat is not explained by geography. Instead, this genetic differentiation is due to the presence of large sex-specific regions in the genomes of both species, but involving different polymorphic sites in each species. Our results therefore indicate rapidly evolving XY sex determination in the two species. Additionally, we found evidence of a large segregating inversion inL. miodon. We found all inversion karyotypes throughout Lake Tanganyika, but the frequencies vary along a north-south gradient, and differ substantially in the introduced Lake Kivu population. We do not find evidence for significant isolation-by-distance, even over the hundreds of kilometers covered by our sampling, but we do find shallow population structure.
A unified framework for dopamine signals across timescales
Authors: Kim HyungGoo R. , Malik Athar N. , Mikhael John G. , Bech Pol , Tsutsui-Kimura Iku , Sun Fangmiao , Zhang Yajun , Li Yulong , Watabe-Uchida Mitsuko , Gershman Samuel J. , Uchida Naoshige 
Published: October 2019

ABSTRACTRapid phasic activity of midbrain dopamine neurons are thought to signal reward prediction errors (RPEs), resembling temporal difference errors used in machine learning. Recent studies describing slowly increasing dopamine signals have instead proposed that they represent state values and arise independently from somatic spiking activity. Here, we developed novel experimental paradigms using virtual reality that disambiguate RPEs from values. We examined the dopamine circuit activity at various stages including somatic spiking, axonal calcium signals, and striatal dopamine concentrations. Our results demonstrate that ramping dopamine signals are consistent with RPEs rather than value, and this ramping is observed at all the stages examined. We further show that ramping dopamine signals can be driven by a dynamic stimulus that indicates a gradual approach to a reward. We provide a unified computational understanding of rapid phasic and slowly ramping dopamine signals: dopamine neurons perform a derivative-like computation over values on a moment-by-moment basis.
Widespread inhibition, antagonism, and synergy in mouse olfactory sensory neurons in vivo
Authors: Inagaki Shigenori , Iwata Ryo , Iwamoto Masakazu , Imai Takeshi 
Published: October 2019

SUMMARYSensory information is selectively or non-selectively inhibited and enhanced in the brain, but it remains unclear whether this occurs commonly at the peripheral stage. Here, we performed two-photon calcium imaging of mouse olfactory sensory neurons (OSNs) in vivo and found that odors produce not only excitatory but also inhibitory responses at their axon terminals. The inhibitory responses remained in mutant mice, in which all possible sources of presynaptic lateral inhibition were eliminated. Direct imaging of the olfactory epithelium revealed widespread inhibitory responses at OSN somata. The inhibition was in part due to inverse agonism toward the odorant receptor. We also found that responses to odor mixtures are often suppressed or enhanced in OSNs: Antagonism was dominant at higher odor concentrations, whereas synergy was more prominent at lower odor concentrations. Thus, odor responses are extensively tuned by inhibition, antagonism, and synergy, at the early peripheral stage, contributing to robust odor representations.
Evolution of Salmonella enterica serotype Typhimurium driven by anthropogenic selection and niche adaptation
Authors: Bawn Matt , Thilliez Gaetan , Kirkwood Mark , Wheeler Nicole , Petrovska Liljana , Dallman Timothy J. , Adriaenssens Evelien M. , Hall Neil , Kingsley Robert A. 
Published: October 2019

AbstractSalmonella enterica serotype Typhimurium (S. Typhimurium) is a leading cause of gastroenteritis and disseminated disease worldwide. Two S. Typhimurium strains (SL1344 and ATCC14028) are widely used to study host-pathogen interactions, yet genotypic variation results in strains with diverse host range, pathogenicity and risk to food safety. A robust fully parsimonious phylogenetic tree constructed from recombination purged variation in the whole genome sequence of 131 diverse strains of S. Typhimurium revealed population structure composed of two high order clades (α and β) and multiple subclades on extended internal branches, that exhibited distinct signatures of host adaptation and anthropogenic selection. Clade α contained a number of subclades composed of strains from well characterized epidemics in domesticated animals, while clade β predominantly contained subclades associated with wild avian species, with the notable exception of a subclade containing the DT204/49 complex. The contrasting epidemiology of α and β strains was reflected in a distinct distribution of antimicrobial resistance (AMR) genes, accumulation of hypothetically disrupted coding sequences (HDCS), and signatures of functional diversification associated with invasiveness of host adapted serotypes. Gene flux was predominantly driven by acquisition, loss or recombination of prophage. The acquisition of large genetic islands (SGI-1 and 4) was limited to two recent pandemic clones (DT104 and monophasic S. Typhimurium ST34) in clade α. Together, our data are consistent with the view that a broad host range common ancestor of S. Typhimurium diversified with clade α lineages remained largely associated with multiple domesticated animal species, while clade β spawned multiple lineages that underwent diversifying selection associated with adaptation to various niches, predominantly in wild avian species.
Open-source 3D printed air-jet for generating monodispersed alginate microhydrogels
Authors: Hadley Dustin J. , Campbell Kevin T. , Gabriel Marina H. , Silva Eduardo A. 
Published: October 2019

AbstractOpen-source designs represent an attractive and new tool for research as it provides both affordable and accessible options to the lab environment. In particular, with the advent of new and cheap additive manufacturing technologies, the open-source design of lab hardware enables others to perform research that would be difficult otherwise. This manuscript describes an air-jet system designed to be open-source and simple to produce with 3D printing. The fully 3D printed air-jet was designed for the generation of hydrogel microbeads of a controllable size. Alginate microbeads were used as a working model, given that it has many promising research applications due to their injectability and highly reproducible properties. A fit definitive design of experiments was performed to determine critical factors affecting diameter, index of dispersity, and circularity of microbeads from this air-jet design. By regulating alginate concentration, air pressure, pump speed, and needle diameter could achieve control over microbeads size from 200-800 µm with low variance. Furthermore, we also demonstrate the potential probiotic research applications of the open-source air-jet through the encapsulation of bacteria in alginate microbeads with controllable degradation. The results of this study exhibit an open-source platform for making microscale biomaterials with controllable properties that can be achieved through budget 3D printers.
The LTB4-BLT1 axis regulates actomyosin and β2 integrin dynamics during neutrophil extravasation
Authors: Subramanian Bhagawat C. , Melis Nicolas , Chen Desu , Wang Weiye , Gallardo Devorah , Weigert Roberto , Parent Carole A. 
Published: October 2019

ABSTRACTThe eicosanoid Leukotriene B4(LTB4) relays chemotactic signals to direct neutrophil migration to inflamed sites through its receptor BLT1. However, the mechanisms by which the LTB4-BLT1 axis relays chemotactic signals during intravascular neutrophil response to inflammation remain unclear. Here, we report that LTB4produced by neutrophils acts as an autocrine/paracrine signal to direct the vascular recruitment, arrest and extravasation of neutrophils in a sterile inflammation model in the mouse footpad. Using Intravital Subcellular Microscopy (ISMic), we reveal that LTB4elicits sustained cell polarization and adhesion responses during neutrophil arrestin vivo. Specifically, LTB4signaling coordinates the dynamic redistribution of non-muscle Myosin IIA (NMIIA) and β2-integrin (Itgb2), which facilitate neutrophil arrest and extravasation. Notably, we also found that neutrophils shed extracellular vesicles (EVs) in the vascular lumen, and that inhibition of EV release blocks LTB4-mediated autocrine/paracrine signaling required for neutrophil arrest and extravasation. Overall, we uncover a novel complementary mechanism by which LTB4relays extravasation signals in neutrophils during early inflammation response.SUMMARYNeutrophils arrest and extravasate from the blood vessels in response to infection and injury. Using intravital subcellular microscopy, Subramanianet al. identify a role for extracellular vesicles-based autocrine/paracrine LTB4-BLT1 signaling in promoting the re-arrangement of actomyosin cytoskeleton and β2-integrin during neutrophil extravasation in live animals.
DNA hydroxymethylation reveals transcription regulation networks and prognostic signatures in multiple myeloma
Authors: Alberge Jean-Baptiste , Magrangeas Florence , Wagner Mirko , Denié Soline , Guérin-Charbonnel Catherine , Campion Loïc , Attal Michel , Avet-Loiseau Hervé , Carell Thomas , Moreau Philippe , Minvielle Stéphane , Sérandour Aurélien A. 
Published: October 2019

AbstractMultiple myeloma (MM) is a plasma cell malignancy that remains challenging to cure despite a substantially improving median survival. During the last decade, DNA copy number variation and gene expression studies have described the pathology and its heterogeneity among patients. Epigenetic modifications play important roles in MM, but they are rarely associated with clinical aspects of the disease. In this epigenomics study, we produced quantifications of genomic 5-methylcytosine (5mC) and of 5-hydroxymethylcytosine (5hmC) as well as genome-wide maps of hydroxymethylation to analyse myeloma cells taken from a cohort of 40 newly diagnosed and homogeneously treated patients. We found 5hmC to be globally depleted in MM compared to normal plasma cells, as well as being reduced in advanced clinical stages of the disease. From the hydroxymethylome data, we observed that remaining 5hmC is organised in large peak clusters and is associated with well-known disease-related genes. Based on their signal correlation, these 5hmC peak clusters can be gathered in 2 regulation networks involving core transcription factors such as IRF4, MYC, PRDM1 and TCF3. By performing paired hydroxymethylomes at diagnosis and at relapse, we found the disease progression to be heterogeneous and patient-specific. We found that the location of 5hmC at tumor suppressor TP53INP1 is associated with better outcome while global high level of 5hmC tends to be associated with better overall survival. Together, our study suggests that 5hmC provides new biological insights of the disease severity and progression, and can be used for retrospective studies.Key Points5hmC is globally depleted in MM and even more in advanced stages of the disease.5hmC is locally detected at transcriptionally active regions of MM where its presence can be associated with survival.
Structural differences in translation initiation between pathogenic trypanosomatids and their mammalian hosts
Authors: Bochler Anthony , Querido Jailson Brito , Prilepskaja Terezie , Soufari Heddy , Simonetti Angelita , Cistia Mayara Lucia Del , Kuhn Lauriane , Ribeiro Aline Rimoldi , Valášek Leoš Shivaya , Hashem Yaser 
Published: October 2019

SUMMARYCanonical mRNA translation in eukaryotes begins with the formation of the 43S pre-initiation complex (PIC). Its assembly requires the binding of several eukaryotic initiation factors (eIF 1, 1A, 2, 3 and 5), Met-tRNAiMet and the small ribosomal subunit (40S). Compared to their mammalian hosts, trypanosomatids present significant structural differences in their 40S suggesting substantial variability in translation initiation. Here we determined the structure of the 43S PIC from Trypanosoma cruzi, the parasite causing the Chagas disease. Our structure shows numerous specific features, such as the variant eIF3 structure and its unique interactions with the large rRNA ESs 9S, 7S and 6S, and the association of a kinetoplastid-specific ~245 kDa DDX60-like helicase. It also revealed the so-far-elusive 40S-binding site of the eIF5 C-terminal domain and the structures of key terminal tails of several conserved eIFs underlying their activities within the PIC. Our results are corroborated by GST-pulldown assays in both human and T. cruzi and mass-spectrometry data.
The STING pathway does not contribute to Pink1/parkin phenotypes in Drosophila
Authors: Lee Juliette J. , Andreazza Simonetta , Whitworth Alexander J. 
Published: October 2019

AbstractMutations in PINK1 and Parkin/PRKN cause the degeneration of dopaminergic neurons in familial forms of Parkinson’s disease but the precise pathogenic mechanisms are unknown. The PINK1/Parkin pathway has been described to play a central role in mitochondrial homeostasis by signaling the targeted destruction of damaged mitochondria, however, how disrupting this process leads to neuronal death until recently was unclear. An elegant study in mice revealed that the loss of Pink1 or Prkn coupled with an additional mitochondrial stress resulted in the aberrant activation of the innate immune signaling, mediated via the cGAS/STING pathway, causing degeneration of dopaminergic neurons and motor impairment. Genetic knockout of Sting was sufficient to completely prevent neurodegeneration and accompanying motor deficits. To determine whether Sting plays a conserved role in Pink1/parkin related pathology, we tested for genetic interactions between Sting and Pink1/parkin in Drosophila. Surprisingly, we found that loss of Sting, or its downstream effector Relish, was insufficient to suppress the behavioral deficits or mitochondria disruption in the Pink1/parkin mutants. Thus, we conclude that phenotypes associated with loss of Pink1/parkin are not universally due to aberrant activation of the STING pathway.
Reactive astrocyte-driven epileptogenesis is induced by microglia initially activated following status epilepticus
Authors: Sano Fumikazu , Shigetomi Eiji , Shinozaki Youichi , Tsuzukiyama Haruka , Saito Kozo , Mikoshiba Katsuhiko , Sugita Kanji , Aihara Masao , Koizumi Schuichi 
Published: October 2019

AbstractExtensive activation of glial cells during a latent period has been well documented in various animal models of epilepsy; however, it remains unknown whether such glial activation is capable of promoting epileptogenesis. Here, we show that temporally distinct activation profiles of microglia and astrocytes collaboratively contribute to epileptogenesis in a drug-induced status epilepticus model. We found that reactive microglia appear first, followed by reactive astrocytes and increased susceptibility to seizures. Pharmacological intervention against microglial activation reduces astrogliosis, aberrant astrocyte Ca2+signaling, and seizure susceptibility. Reactive astrocytes exhibit larger Ca2+signals mediated by IP3R2, whereas deletion of this type of Ca2+signaling reduces seizure susceptibility after status epilepticus. Together, our findings indicate that the sequential activation of glial cells constitutes a cause of epileptogenesis after status epilepticus.
Radiologic Evaluation of the Influence of Cleft Type on Nasal Dorsum Growth
Authors: Pu Lingling , Liu Renkai , Shi Bing , Low David W , Li Chenghao 
Published: October 2019

AbstractPurposeThe study was designed to evaluate whether intrinsic morphological characteristics of the nasal dorsum are affected by cleft type, specifically cleft lip only (CL) and cleft lip with cleft palate(CL/P).Methods576 cleft patients (278 CL only, 298 CL/P), and 333 individuals without orofacial clefts were retrospectively enrolled. Lateral cephalometric radiographs of all individuals were taken to evaluate the nasal length and nasal dorsum height. Dunn’s test was used to analyze the difference (p< 0.001).ResultsIn CL and control, the angulation of the nasal bone and nasal dorsum increase by age similarly (5y-18y, p>0.05). In CL, the total dorsal length is significantly shorter (5y-18y,p<0.001). Although the upper nasal dorsum is similar (except in 5y-6y), the lower nasal dorsum is shorter (5y-18y,p<0.001).In CLP, there is no significant difference in the nasal bone angle compared with controls between 5y-7y. However, it develops insufficiently as children grow (8y-18y,p<0.001). The nasal dorsum angle is notably smaller (5y-18y, p<0.001). Nasal bone length is not significantly different from control at all stages except during ages 11y-13y (p<0.05). Total nasal dorsal length is similar to the control at skeletal maturity (17y-18y,p>0.05), although it is shorter during 8y to 16y (p<0.05). The upper nasal dorsum is overdeveloped (14y-18y,p<0.05), whereas the lower nasal dorsum is underdeveloped (5y-18y,p<0.001).ConclusionCL inhibits the growth of nasal dorsum length, leading to short nose deformity. CL/P patients are prone to saddle-nose deformity because of the diminished nasal height (decreased nasal angle).
Proximity proteomics in a marine diatom reveals a putative cell surface-to-chloroplast iron trafficking pathway
Authors: Turnšek Jernej , Brunson John K. , Martinez Viedma Maria del Pilar , Deerinck Thomas J. , Horák Aleš , Oborník Miroslav , Bielinski Vincent A. , Allen Andrew E. 
Published: October 2019

AbstractIron is a biochemically critical metal cofactor in enzymes involved in photosynthesis, cellular respiration, nitrate assimilation, nitrogen fixation, and reactive oxygen species defense. Marine microeukaryotes have evolved a phytotransferrin-based iron uptake system to cope with iron scarcity, a major factor limiting primary productivity in the global ocean. Diatom phytotransferrin is endocytosed, however proteins downstream of this environmentally ubiquitous iron receptor are unknown. We applied engineered ascorbate peroxidase APEX2-based subcellular proteomics to catalog proximal proteins of phytotransferrin in the model marine diatomPhaeodactylum tricornutum. Proteins encoded by poorly characterized iron-sensitive genes were identified including three that are expressed from a chromosomal gene cluster. Two of them showed unambiguous colocalization with phytotransferrin adjacent to the chloroplast. Further phylogenetic, domain, and biochemical analyses suggest their involvement in intracellular iron processing. Proximity proteomics holds enormous potential to glean new insights into iron acquisition pathways and beyond in these evolutionarily, ecologically, and biotechnologically important microalgae.
Niche-inspired synthetic matrices for epithelial organoid culture
Authors: Hernandez-Gordillo Victor , Kassis Timothy , Lampejo Arinola , Choi GiHun , Gamboa Mario E. , Gnecco Juan S. , Breault David T. , Carrier Rebecca , Griffith Linda G. 
Published: October 2019

AbstractEpithelial organoids are now an important tool in fields ranging from regenerative medicine to drug discovery. Organoid culture requires Matrigel, a complex, tumor-derived, extracellular matrix. An alternative completely synthetic matrix could improve culture reproducibility, clarify mechanistic phenomena, and enable applications involving human implantation. Here, we designed synthetic matrices with tunable biomolecular and biophysical properties that allowed us to identify critical gel parameters in organoid formation. Inspired by known epithelial integrin expression in the proliferative niche of the human intestine, we identified an α2β1 integrin-binding peptide as a critical component of the synthetic matrix that supports human duodenal colon and endometrial organoid propagation. We show that organoids emerge from single cells, retain their proliferative capacity, are functionally responsive to basolateral stimulation and have correct apicobasal polarity upon induction of differentiation. The local biophysical presentation of the cues, rather than bulk mechanical properties, appears to be the dominant parameter governing epithelial cell proliferation and organoid formation in the synthetic matrix.
Cannabis use is associated with increased levels of soluble gp130 in schizophrenia but not in bipolar disorder
Authors: Szabo Attila , Akkouh Ibrahim A. , Ueland Thor , Lagerberg Trine Vik , Dieset Ingrid , Bjella Thomas , Aukrust Pål , Le Hellard Stephanie , Stavrum Anne-Kristin , Melle Ingrid , Andreassen Ole A. , Djurovic Srdjan 
Published: October 2019

ABSTRACTThe complex effects of plant cannabinoids on human physiology is not yet fully understood, but include a wide spectrum of effects on immune modulation. The immune system and its inflammatory effector pathways are recently emerging as possible causative factors in psychotic disorders. The present study aimed to investigate whether self-administered cannabis use was associated with changes in circulating immune and neuroendocrine markers in schizophrenia (SCZ, n=401) and bipolar disorder patients (BD, n=242). A screening of 13 plasma markers reflecting different inflammatory pathways was performed in SCZ and BD patients after subdividing each group into cannabis user and non-user subgroups. We found that i) soluble gp130 (sgp130) concentrations were significantly elevated among cannabis users in the SCZ group (p=0.002) after multiple testing correction, but not in BD. ii) Nominally significant differences were observed in the levels of IL-1RA (p=0.0059), YKL40 (p=0.0069), CatS (p=0.013), sTNFR1 (p=0.031), and BDNF (p=0.020), where these factors exhibited higher plasma levels in cannabis user SCZ patients than in non-users. iii) These differences in systemic levels were not reflected by altered mRNA expression of genes encoding sgp130, IL-1RA, YKL40, CatS, sTNFR1, and BDNF in whole blood. In sum, our results show that cannabis self-administration is associated with markedly higher sgp130 levels in SCZ, but not in BD, and that this phenomenon is independent of the modulation of peripheral immune cells. These findings warrant further investigation into the potential neuroimmune, anti-inflammatory, and biobehavioral-cognitive effects of cannabis use in SCZ.