bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immune Relevant and Immune Deficient Mice: Options and Opportunities in Translational Research
Authors: Radaelli Enrico , Santagostino Sara F , Sellers Rani S , Brayton Cory F 
Published: January 2019

AbstractIn 1989 ILAR published a list and description of immunodeficient rodents used in research. Since then, advances in understanding of molecular mechanisms; recognition of genetic, epigenetic microbial, and other influences on immunity; and capabilities in manipulating genomes and microbiomes have increased options and opportunities for selecting mice and designing studies to answer important mechanistic and therapeutic questions. Despite numerous scientific breakthroughs that have benefitted from research in mice, there is debate about the relevance and predictive or translational value of research in mice. Reproducibility of results obtained from mice and other research models also is a well-publicized concern. This review summarizes resources to inform the selection and use of immune relevant mouse strains and stocks, aiming to improve the utility, validity, and reproducibility of research in mice. Immune sufficient genetic variations, immune relevant spontaneous mutations, immunodeficient and autoimmune phenotypes, and selected induced conditions are emphasized.
En-Bloc U-Shaped Osteotomy of the Mandible and Chin for the Correction of a Prominent Mandibular Angle With Long Chin
Authors: Lai Chenzhi , Jin Xiaolei , Zong Xianlei , Song Guodong 
Published: January 2019

Background:
Lower face contouring surgery has become a popular aesthetic surgery in East Asian countries. Various surgical methods have been used to improve lower face aesthetics. When a patient has a wide as well as long lower face, procedures like chin polishing or T-type osteotomy are traditionally performed, but these surgical methods have several disadvantages. The authors devised a simple and reliable method to correct the wide and long lower face, without the complications associated with the traditional methods.

Methods:
From July 2015 to January 2018, 30 patients with a prominent mandibular angle, long chin, and no malocclusion underwent en-bloc mandibular U-shaped osteotomy through an oral incision, in order to shorten the mandibular angle, body of the mandible, and the chin, and to improve the facial contour. The authors assessed the effectiveness of surgery through comparisons between pre- and postoperative radiographs, patient satisfaction, and surgical complications in the postoperative period.

Results:
It was observed that all oral incisions healed by primary intention, and did not develop hematoma, infection, or osteonecrosis. Lower lip numbness occurred in 16 patients. After 6 to 12 months, all patients showed complete recovery from the numbness. All the patients were satisfied with their appearance after surgery.

Conclusions:
En-bloc mandibular U-shaped osteotomy is an improved form of mandibular surgery. The osteotomy line involves the whole mandible, which makes the length and width of the mandible considerably smaller. This surgery can effectively correct a prominent mandibular angle with long chin.
Conjunction or co-activation? A multi-level MVPA approach to task set representations
Authors: Deraeve James , Vassena Eliana , Alexander William H. 
Published: January 2019

AbstractWhile representing and maintaining rules in order to govern behavior is a critical function of the brain, it remains an open question as to how collections of rules - task sets - are represented in cortex. One possibility is that task sets are represented as the co-activation of representations of the simple rules from which a task set is composed. Alternatively, task sets could be encoded in a conjunctive manner as the unique combination of rules that belong to a task set. Using a novel multi-level MVPA approach in combination with fMRI, we attempted to answer both “where” and “how” task sets are represented in the brain. Subjects performed a delayed match-to-sample task using task sets composed of multiple, partially overlapping rules that governed which feature dimensions subjects should attend to, and MVPA was used to identify regions that encoded task set information. We identified voxels most relevant for classifying task sets, and, using these voxels as input to a second MVPA analysis, were able to identify regions in prefrontal cortex with activity consistent with co-active representation, while activity in visual cortex was consistent with conjunctive representation. These results highlight the utility of feature selection methods in neuroimaging analyses.
SpoIVA-SipL complex formation is essential forClostridioides difficilespore assembly
Authors: Touchette Megan H. , Puebla Hector Benito de la , Ravichandran Priyanka , Shen Aimee 
Published: January 2019

AbstractSpores are the major infectious particle of the Gram-positive nosocomial pathogen,Clostridioides(formerlyClostridium)difficile, but the molecular details of how this organism forms these metabolically dormant cells remain poorly characterized. The composition of the spore coat inC. difficilediffers markedly from that defined in the well-studied organism,Bacillus subtilis, with only 25% of the ~70 spore coat proteins being conserved between the two organisms, and only 2 of 9 coat assembly (morphogenetic) proteins defined inB. subtilishaving homologs inC. difficile.We previously identified SipL as a clostridia-specific coat protein essential for functional spore formation. Heterologous expression analyses inE. colirevealed that SipL directly interacts withC. difficileSpoIVA, a coat morphogenetic protein conserved in all spore-forming organisms, through SipL’s C-terminal LysM domain. In this study, we show that SpoIVA-SipL binding is essential forC. difficilespore formation and identify specific residues within the LysM domain that stabilize this interaction. Fluorescence microscopy analyses indicate that binding of SipL’s LysM domain to SpoIVA is required for SipL to localize to the forespore, while SpoIVA requires SipL to promote encasement of SpoIVA around the forespore. Since we also show that clostridial LysM domains are functionally interchangeable at least inC. difficile, the basic mechanism for SipL-dependent assembly of clostridial spore coats may be conserved.ImportanceThe metabolically dormant spore-form of the major nosocomial pathogen,Clostridioides difficile, is its major infectious particle. However, the mechanisms controlling the formation of these resistant cell types are not well understood, particularly with respect to its outermost layer, the spore coat. We previously identified two spore morphogenetic proteins inC. difficile: SpoIVA, which is conserved in all spore-forming organisms, and SipL, which is conserved only in the Clostridia. Both SpoIVA and SipL are essential for heat-resistant spore formation and directly interact through SipL’s C-terminal LysM domain. In this study, we demonstrate that the LysM domain is critical for SipL and SpoIVA function, likely by helping recruit SipL to the forespore during spore morphogenesis. We further identified residues within the LysM domain that are important for binding SpoIVA and thus functional spore formation. These findings provide important insight into the molecular mechanisms controlling the assembly of infectiousC. difficilespores.
LipoGlo: A sensitive and specific reporter of atherogenic lipoproteins
Authors: Thierer James H. , Ekker Stephen C. , Farber Steven A. 
Published: January 2019

ABSTRACTApolipoprotein-B (APOB) is the structural component of atherogenic lipoproteins, lipid-rich particles that drive atherosclerosis by accumulating in the vascular wall. As atherosclerotic cardiovascular disease is the leading cause of death worldwide, there is an urgent need to develop new strategies to prevent lipoproteins from causing vascular damage. Here we report the LipoGlo system, which uses a luciferase enzyme (NanoLuc) fused to ApoB to monitor several key determinants of lipoprotein atherogenicity including particle abundance, size, and localization. Using LipoGlo, we are able to comprehensively characterize the lipoprotein profile of individual larval zebrafish and collect the first images of atherogenic lipoprotein localization in an intact organism. We discover multiple unexpected extravascular lipoprotein localization patterns, as well as identifypla2g12bas a potent regulator of lipoprotein size. ApoB-fusion proteins thus represent a uniquely sensitive and specific approach to study atherogenic lipoproteins and their genetic and small molecule modifiers.
LINE-1 retrotransposition impacts the genome of human pre-implantation embryos and extraembryonic tissues
Authors: Muñoz-Lopez Martin , Vilar Raquel , Philippe Claude , Rahbari Raheleh , Richardson Sandra R. , Andres-Anton Miguel , Widmann Thomas , Cano David , Cortes Jose L. , Rubio-Roldan Alejandro , Guichard Etienne , Heras Sara R. , Sanchez-Luque Francisco J. , Morell Maria , Aguilar Elisabet , Garcia-Cañadas Marta , Sanchez Laura , Macia Angela , Vilches Pedro , Nieto-Perez Maria Concepcion , Gomez-Martin Antonio , Gonzalez-Alzaga Beatriz , Aguilar-Garduno Clemente , Ewing Adam D. , Lacasana Marina , Alvarez Ignacio S. , Badge Richard , Faulkner Geoffrey J. , Cristofari Gael , Garcia-Perez Jose L. 
Published: January 2019

ABSTRACTLong Interspersed Element 1 (LINE-1/L1) is an abundant retrotransposon that has greatly impacted human genome evolution. LINE-1s are responsible for the generation of millions of insertions in the current human population. The characterization of sporadic cases of mosaic individuals carrying pathogenic L1-insertions, suggest that heritable insertions occurs during early embryogenesis. However, the timing and potential genomic impact of LINE-1 mobilization during early embryogenesis is unknown. Here, we demonstrate that inner cell mass of human pre-implantation embryos support the expression and retrotransposition of LINE −1s. Additionally, we show that LINE-1s are expressed in trophectoderm cells of embryos, and identify placenta-restricted endogenous LINE-1 insertions in newborns. Using human embryonic stem cells as a model of post-implantation epiblast cells, we demonstrate ongoing LINE-1 retrotransposition, which can impact expression of targeted genes. Our data demonstrate that LINE-1 retrotransposition starts very shortly after fertilization and may represent a previously underappreciated factor in human biology and disease.
A model for the spatio-temporal design of gene regulatory circuits
Authors: Stoof Ruud , Wood Alexander , Goñi-Moreno Ángel 
Published: January 2019

AbstractThe design of increasingly complex gene regulatory networks relies upon mathematical modelling to link the gap that goes from conceptualisation to implementation. An overarching challenge is to update modelling abstractions and assumptions as new mechanistic information arises. Although models of bacterial gene regulation are often based on the assumption that the role played by intracellular physical distances between genetic elements is negligible, it has been shown that bacteria are highly ordered organisms, compartmentalizing their vital functions in both time and space. Here, we analysed the dynamical properties of regulatory interactions by explicitly modelling spatial constraints. Key to the model is the combined search by a regulator for its target promoter via 1D sliding along the chromosome and 3D diffusion through the cytoplasm. Moreover, this search was coupled to gene expression dynamics, with special attention to transcription factor-promoter interplay. As a result, promoter activity within the model depends on its physical separation from the regulator source. Simulations showed that by modulating the distance between DNA components in the chromosome, output levels changed accordingly. Finally, previous experimental results with engineered bacteria in which this distance was minimized or enlarged were successfully reproduced by the model. This suggests that the spatial specification of the circuit alone can be exploited as a design parameter to select programmable output levels.
PRISMOID: a comprehensive 3D structure database for post-translational modifications and mutations with functional impact
Authors: Li Fuyi , Fan Cunshuo , Marquez-Lago Tatiana T. , Leier André , Revote Jerico , Jia Cangzhi , Zhu Yan , Ian Smith A. , Webb Geoffrey I. , Liu Quanzhong , Wei Leyi , Li Jian , Song Jiangning 
Published: January 2019

AbstractPost-translational modifications (PTMs) play very important roles in various cell signalling pathways and biological process. Due to PTMs’ extremely important roles, many major PTMs have been thoroughly studied, while the functional and mechanical characterization of major PTMs is well-documented in several databases. However, most currently available databases mainly focus on protein sequences, while the real 3D structures of PTMs have been largely ignored. Therefore, studies of PTMs 3D structural signatures have been severely limited by the deficiency of the data. Here, we develop PRISMOID, a novel publicly available and free 3D structure database for a wide range of PTMs. PRISMOID represents an up-to-date and interactive online knowledge base with specific focus on 3D structural contexts of PTMs sites and mutations that occur on PTMs and in the close proximity of PTM sites with functional impact. The first version of PRISMOID encompasses 17,145 non-redundant modification sites on 3,919 related protein 3D structure entries pertaining to 37 different types of PTMs. Our entry web page is organized in a comprehensive manner, including detailed PTM annotation on the 3D structure and biological information in terms of mutations affecting PTMs, secondary structure features and per-residue solvent accessibility features of PTM sites, domain context, predicted natively disordered regions and sequence alignments. In addition, high-definition JavaScript packages are employed to enhance information visualization in PRISMOID. PRISMOID equips a variety of interactive and customizable search options and data browsing functions; these capabilities allow users to access data via keyword, ID, and advanced options combination search in an efficient and user-friendly way. A download page is also provided to enable users to download the SQL file, computational structural features, and PTM sites’ data. We anticipate PRISMOID will swiftly become an invaluable online resource, assisting both biologists and bioinformaticians to conduct experiments and develop applications supporting discovery efforts in the sequence-structural-functional relationship of PTMs and providing important insight into mutations and PTM sites interaction mechanisms. The PRISMOID database is freely accessible athttp://prismoid.erc.monash.edu/. The database and web interface are implemented in MySQL, JSP, JavaScript, and HTML with all major browsers supported.
Synaptonemal complex proteins direct and constrain the localization of crossover-promoting proteins duringCaenorhabditis elegansmeiosis
Authors: Cahoon Cori K. , Helm Jacquellyn M. , Libuda Diana E. 
Published: January 2019

AbstractCrossovers (COs) between homologous chromosomes are critical for meiotic chromosome segregation and form in the context of the synaptonemal complex (SC), a meiosis-specific structure that assembles between aligned homologs. DuringCaenorhabditis elegansmeiosis, central region components of the SC (SYP proteins) are essential to repair double-strand DNA breaks (DSBs) as COs, but the roles of these SYP proteins in promoting CO formation are poorly understood. Here, we investigate the relationships between the SYP proteins and conserved CO-promoting factors by examining the immunolocalization of these factors in meiotic mutants where SYP proteins are absent, reduced, or mis-localized. Although COs do not form insypnull mutants, CO-promoting proteins COSA-1, MSH-5, and ZHP-3 nevertheless become co-localized at a variable number of DSB-dependent sites during late prophase, reflecting an inherent affinity of these factors for DSB repair sites. In contrast, in mutants where SYP proteins are present but form aggregates or display abnormal synapsis, CO-promoting proteins consistently track with SYP-1 localization. Moreover, CO-promoting proteins usually localize to a single site per SYP-1 structure, even in SYP aggregates or in mutants where SC forms between sister-chromatids, suggesting that CO regulation occurs within these structures. Further, we find that sister chromatids in the meiotic cohesin mutantrec-8require both CO-promoting proteins and the SC to remain connected. Taken together, our findings support a model in which SYP proteins promote CO formation by directing and constraining the localization of CO-promoting factors to ensure that CO maturation occurs only between properly aligned homologous chromosomes.Article SummaryErrors during meiosis are the leading cause of birth defects and miscarriages in humans. Thus, the coordinated control of meiosis events is critical for the faithful inheritance of the genome each generation. The synaptonemal complex (SC) is a meiosis-specific structure that assembles between homologs chromosomes and is critical for the establishment and regulation of crossovers, which ensure the accurate segregation of the homologous chromosomes at meiosis I. Here we show that the SC proteins function to regulate crossovers by directing and constraining the localization of proteins involved in promoting the formation of crossovers.
Development of Human Neuroblastomas in Mouse-Human Neural Crest Chimeras
Authors: Cohen Malkiel A. , Zhang Shupei , Sengupta Satyaki , Ma Haiting , Horton Brendan , Bell George W. , George Rani E. , Spranger Stefani , Jaenisch Rudolf 
Published: January 2019

SummaryNeuroblastoma (NB), derived from the neural crest (NC), is the most common pediatric extracranial solid tumor. Here we establish a platform that allows studying human NBs in mouse-human NC chimeras. Chimeric mice were produced by injecting human NC cells carrying NB relevant oncogenesin-uterointo gastrulating mouse embryos. The mice developed tumors composed of a heterogenous cell population that closely resembled that seen in primary NBs of patients but were significantly different from homogenous tumors formed in xenotransplantation models. The human tumors emerged in immunocompetent hosts and were extensively infiltrated by mouse cytotoxic T cells reflecting a vigorous host anti-tumor immune response. However, the tumors blunted the immune response by inducing infiltration of regulatory T cells and expression of immune checkpoints similar to escape mechanisms seen in human cancer patients. Thus, this experimental platform allows studying human tumor initiation, progression, manifestation and tumor – immune-system interactions in an animal model system.
The differential contribution of pacemaker neurons to synaptic transmission in the pyloric network of the Jonah crab, Cancer borealis
Authors: Martinez Diana , Santin Joseph M. , Schulz David , Nadim Farzan 
Published: January 2019

AbstractMany neurons receive synchronous input from heterogeneous presynaptic neurons with distinct properties. An instructive example is the crustacean stomatogastric pyloric circuit pacemaker group, consisting of the anterior burster (AB) and pyloric dilator (PD) neurons, which are active synchronously and exert a combined synaptic action on most pyloric follower neurons. Although the stomatogastric system of the crab Cancer borealis has become a preferred model system for exploration of cellular and synaptic basis of circuit dynamics, in this species, the identity of the PD neuron neurotransmitter and its contribution to the total pacemaker group synaptic output remain unexplored. We examined the synaptic properties of the crab PD neuron using a combination of single cell mRNA analysis, electrophysiology and pharmacology. The crab PD neuron expresses high levels of choline acetyltransferase and the vesicular acetylcholine transporter mRNAs, hallmarks of cholinergic neurons. Conversely, the AB neuron does not express either of these cholinergic markers, and expresses high levels of vesicular glutamate transporter mRNA, consistent with a glutamatergic phenotype. Notably, in the combined synapses to the LP and PY neurons, the major contribution is from the glutamatergic AB neuron and only between 25-30% of the synaptic strength is due to the PD neuron. However, there was no difference between the short-term synaptic plasticity in the total pacemaker synapse compared to that of the PD neuron alone. These findings provide a guide for similar explorations of heterogeneous synaptic connections in other systems and a baseline in this system for the exploration of the differential influence of neuromodulators.
Ecological and microbiological diversity of chigger mites, including vectors of scrub typhus, on small mammals across stratified habitats in Thailand
Authors: Chaisiri Kittipong , Gill A. Christina , Stekolnikov Alexandr A. , Hinjoy Soawapak , McGarry John W. , Darby Alistair C. , Morand Serge , Makepeace Benjamin L. 
Published: January 2019

AbstractScrub typhus, caused by a bacterial pathogen (Orientia spp.), is a potentially life-threatening febrile illness widely distributed in the Asia-Pacific region and is emerging elsewhere. The infection is transmitted by the larval stage of trombiculid mites (“chiggers”) that often exhibit low host specificity. Here, we present an analysis of chigger ecology for 38 species sampled from 11 provinces of Thailand and microbiomes for eight widespread species. In total, >16 000 individual chiggers were collected from 1 574 small mammal specimens belonging to 18 species across four horizontally-stratified habitat types. Chigger species richness was positively associated with higher latitudes, dry seasonal conditions, and host maturity; but negatively associated with increased human land use. Human scrub typhus incidence was found to be positively correlated with chigger species richness. The bacterial microbiome of chiggers was highly diverse, with Sphingobium, Mycobacterium, Neisseriaceae and various Bacillales representing the most abundant taxa. Only Leptotrombidium deliense was found to be infected with Orientia. β-diversity, but not α-diversity, was significantly different between chigger species and geographic regions, although not between habitat types. This first field survey of the chigger microbiome provides a framework for future studies on interactions between pathogens and other symbionts in these understudied vectors.