bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hippocampal Sulcus Remnant: Common Finding in Nonelderly Adults on Ultra-High-Resolution 7T Magnetic Resonance Imaging
Authors: Yamashita Koji , Zong Xiaopeng , Hung Sheng-Che , Lin Weili , Castillo Mauricio 
Published: December 2019

Objective
The objective of this study was to investigate the frequency of hippocampal sulcus remnants (HSRs) in nonelderly adults using ultra-high-resolution 7T magnetic resonance (MR) images and their imaging features.

Methods
A total of 33 healthy adults underwent 7T MR, and multiplanar images of 66 temporal lobes were reviewed independently by 2 neuroradiologists. The detectability of the HSR was calculated. In addition, the interobserver agreement on the rating scale was evaluated using the κ statistic.

Results
Both observers identified HSRs with 7T MR images in all subjects. Excellent interobserver agreement was shown (κ = 1.0). The shape of HSRs was variable (spot-like, curvilinear, ovoid, or beaded appearance). Volumes of the HSRs were not correlated with age.

Conclusions
Hippocampal sulcus remnants are commonly seen in healthy nonelderly adults using 7T MR imaging. Accurate diagnosis of HSR based on the microanatomy of hippocampus makes it easier to differentiate them from lesions, and it may help prevent unnecessary treatment.
Organellar protein multi-functionality and phenotypic plasticity in plants
Authors: Mackenzie Sally A. , Kundariya Hardik 
Published: December 2019

With the increasing impact of climate instability on agricultural and ecological systems has come a heightened sense of urgency to understand plant adaptation mechanisms in more detail. Plant species have a remarkable ability to disperse their progeny to a wide range of environments, demonstrating extraordinary resiliency mechanisms that incorporate epigenetics and transgenerational stability. Surprisingly, some of the underlying versatility of plants to adapt to abiotic and biotic stress emerges from the neofunctionalization of organelles and organellar proteins. We describe evidence of possible plastid specialization and multi-functional organellar protein features that serve to enhance plant phenotypic plasticity. These features appear to rely on, for example, spatio-temporal regulation of plastid composition, and unusual interorganellar protein targeting and retrograde signalling features that facilitate multi-functionalization. Although we report in detail on three such specializations, involving MSH1, WHIRLY1 and CUE1 proteins inArabidopsis, there is ample reason to believe that these represent only a fraction of what is yet to be discovered as we begin to elaborate cross-species diversity. Recent observations suggest that plant proteins previously defined in one context may soon be rediscovered in new roles and that much more detailed investigation of proteins that show subcellular multi-targeting may be warranted.This article is part of the theme issue ‘Linking the mitochondrial genotype to phenotype: a complex endeavour’.
Engineering synthetic mini-chromosomes to study chromosome segregation in budding yeast
Authors: Jonsson Katarina , Zulkower Valentin , Robertson Daniel , Cai Yizhi , Marston Adele 
Published: December 2019

Chromosomes need to be replicated and partitioned into daughter cells during cellular division. Failure to do so leads to aneuploidy, which has been linked to medical conditions such as cancer. Cohesin, a ring-shaped protein complex, holds the replicated sister chromatids together to ensure their accurate segregation. In Saccharomyces cerevisiae a large pool of cohesin is loaded at centromeres. Introducing the centromeric sequence to circular and linear DNA has been exploited to allow propagation of extra-chromosomal DNA. However, these extra-chromosomal DNA do not segregate as well as endogenous chromosomes and the reasons for this are unknown. Interestingly, small circular chromosomes are more stable than their linear counterparts. Furthermore, the stability of linear chromosomes increases with chromosome length. The DNA sequence itself appears to be important as linear chromosomes containing endogenous DNA are more stable than chromosomes derived from artificial DNA of similar lengths. During our project, we sought to identify cis-acting DNA elements, other than the centromere, that are important for chromosome segregation.
We have developed a synthetic biology approach to engineer a library of synthetic circular and linear chromosomes of various lengths containing unnatural DNA (designed to lack features of known elements such as transcription units). These chromosomes act as a “blank canvas” where candidate DNA elements are introduced to test their functionality. Our design, build and test cycle has allowed us to determine how chromosome length, circularization and DNA sequence influence chromosome segregation and the minimal requirements for building the optimal synthetic chromosome. Our latest findings will be presented.
Niche-selective inhibition of pathogenic Th17 cells by targeting metabolic redundancy
Authors: Wu Lin , Hollinshead Kate E.R. , Hao Yuhan , Au Christy , Kroehling Lina , Ng Charles , Lin Woan-Yu , Li Dayi , Silva Hernandez Moura , Shin Jong , Lafaille Juan J. , Possemato Richard , Pacold Michael E. , Papagiannakopoulos Thales , Kimmelman Alec C. , Satija Rahul , Littman Dan R. 
Published: December 2019

SummaryTargeting glycolysis has been considered therapeutically intractable owing to its essential housekeeping role. However, the context-dependent requirement for individual glycolytic steps has not been fully explored. We show that CRISPR-mediated targeting of glycolysis in T cells in mice results in global loss of Th17 cells, whereas deficiency of the glycolytic enzyme glucose phosphate isomerase (Gpi1) selectively eliminates inflammatory encephalitogenic and colitogenic Th17 cells, without substantially affecting homeostatic microbiota-specific Th17 cells. In homeostatic Th17 cells, partial blockade of glycolysis upon Gpi1 inactivation was compensated by pentose phosphate pathway flux and increased mitochondrial respiration. In contrast, inflammatory Th17 cells experience a hypoxic microenvironment known to limit mitochondrial respiration, which is incompatible with loss of Gpi1. Our study suggests that inhibiting glycolysis by targeting Gpi1 could be an effective therapeutic strategy with minimum toxicity for Th17-mediated autoimmune diseases, and, more generally, that metabolic redundancies can be exploited for selective targeting of disease processes.
CsHscB as a novel TLR2 agonist from carcinogenic liver fluke Clonorchis sinensis modulates host immune response
Authors: Yan Chao , Fan Fang , Zhang Yu-Zhao , Wu Jing , Dong Xin , Liu Hai-Liang , Fan Chun-Yang , Yu Qian , Wang Liang , Li Xiang-Yang , Wang Yu-Gang , Chen Jia-Xu , Tang Ren-Xian , Zheng Kui-Yang 
Published: December 2019

AbstractClonorchis sinensis-a fluke dwelling on the intrahepatic bile ducts causes clonorchiasis. During C. sinensis infection, worm-host interaction results in activation of PRRs and further triggers immune responses which determine the outcome of infection. However, the mechanisms by which pathogen-associated molecules patterns from C. sinensis interacted with TLRs were poorly understood. In the present study, we identified a ∼34 kDa lipoprotein CsHscB from C. sinensis which physically bound with TLR2. We also found that recombinant CsHscB (rCsHscB) potently activated macrophage to express various proteins including TLR2, CD80, MHCII, and cytokines like IL-6, TNF-α, and IL-10 in a TLR2-dependent manner but rCsHscB failed to induce IL-10 in macrophages from Tlr2-/- mice. Moreover, ERK1/2 activation was required for rCsHscB-induced IL-10 production in macrophages. In vivo study revealed that rCsHscB triggered a high induction of IL-10 in the wild-type (WT) but not in Tlr2-/- mice. Our data thus demonstrate that rCsHscB from C. sinensis is an unidentified TLR2 agonist with immune regulatory activities, and may have some therapeutic implications in future beyond parasitology.
An upstream open reading frame represses translation of chicken PPARγ transcript variant 1
Authors: Chu Yankai , Huang Jiaxin , Ma Guangwei , Cui Tingting , Yan Xiaohong , Li Hui , Wang Ning 
Published: December 2019

AbstractPeroxisome proliferator-activated receptor γ (PPARγ) is a master regulator of adipogenesis. The PPARγ gene produces various transcripts with different 5′-untranslated regions (5′ UTRs) because of alternative promoter usage and splicing. The 5′ UTR plays important roles in posttranscriptional gene regulation. However, to date, the regulatory role and underlying mechanism of 5′ UTRs in the posttranscriptional regulation of PPARγ expression remain largely unclear. In this study, we investigated the effects of 5′ UTRs on posttranscriptional regulation using reporter assays. Our results showed that the five PPARγ 5′ UTRs exerted different effects on reporter gene activity. Bioinformatics analysis showed that chicken PPARγ transcript 1 (PPARγ1) possessed an upstream open reading frame (uORF) in its 5′ UTR. Mutation analysis showed that a mutation in the uORF led to increased Renilla luciferase activity and PPARγ protein expression, but decreased Renilla luciferase and PPARγ1 mRNA expression. mRNA stability analysis using real-time RT-PCR showed that the uORF mutation did not interfere with mRNA stability, but promoter activity analysis of the cloned 5′ UTR showed that the uORF mutation reduced promoter activity. Furthermore, in vitro transcription/translation assays demonstrated that the uORF mutation markedly increased the translation of PPARγ1 mRNA. Collectively, our results indicate that the uORF represses the translation of chicken PPARγ1 mRNA.
Oxytocin has sex-specific effects on social behaviour and hypothalamic oxytocin immunoreactive cells but not hippocampal neurogenesis in adult rats
Authors: Duarte-Guterman Paula , Lieblich Stephanie E. , Qiu Wansu , Splinter Jared E.J. , Go Kimberly A. , Casanueva-Reimon Laura , Galea Liisa A.M. 
Published: December 2019

AbstractOxytocin regulates social behaviours, pair bonding and hippocampal neurogenesis but most studies have used adult males. Our study investigated the effects of oxytocin on social investigation and adult hippocampal neurogenesis in male and female rats. Oxytocin has poor penetration of the blood-brain barrier, therefore we tested a nanoparticle drug, TRIOZANTM (Ovensa Inc.), which permits greater blood-brain-barrier penetration. Adult male and female rats were injected daily (i.p.) for 10 days with either: oxytocin in PBS (0.5 or 1.0 mg/kg), oxytocin in TRIOZANTM (0.5 or 1.0 mg/kg), or vehicle (PBS) and tested for social investigation. Oxytocin decreased body mass and increased social investigation and number of oxytocin-immunoreactive cells in the supraoptic nucleus (SON) of the hypothalamus in male rats only. In both sexes, oxytocin decreased the number of immature neurons (doublecortin+ cells) in the ventral hippocampus and reduced plasma 17β-estradiol levels in a dose- and delivery-dependent way. Oxytocin in TRIOZANTM reduced sedation observed post-injection and increased some central effects (oxytocin levels in the hypothalamus and ventral hippocampus neurogenesis) relative to oxytocin in PBS indicating that the nanoparticle may be used as an alternative brain delivery system. We showed that oxytocin has sex-specific effects on social investigation, body mass, sedation, and the oxytocin system. In contrast, similar effects were observed in both sexes in neurogenesis and plasma 17β-estradiol. Our work suggests that sex differences in oxytocin regulation of brain endpoints is region-specific (hypothalamus versus hippocampus) and that oxytocin does not promote social investigation in females.
Cancer modeling in colorectal organoids reveals intrinsic differences between oncogenic RAS and BRAF variants
Authors: Post Jasmin B. , Hami Nizar , Lohuis Jeroen , van de Ven Marieke , de Korte-Grimmerink Renske , Stangl Christina , Stelloo Ellen , Verlaan Ingrid , van Rheenen Jacco , Snippert Hugo J.G. 
Published: December 2019

AbstractColorectal cancers (CRCs) with oncogenic mutations in RAS and BRAF are associated with anti-EGFR therapy resistance. Consequently, all RAS mutant CRC patients are being excluded from this therapy. However, heterogeneity in drug response has been reported between RAS mutant CRC patients. It is poorly understood to what extent such differences are derived from different genetic backgrounds or intrinsic differences between the various RAS pathway mutations. Therefore, using CRISPR technology we generated an isogenic panel of patient-derived CRC organoids with various RAS pathway mutations (i.e. KRASG12D, BRAFV600E, KRASG13D and NRASG12D). All RAS pathway mutants promote ERK activation and tumor growth. However, KRASG12D and BRAFV600E mutations in particular conferred robust resistance to anti-EGFR therapy, both in vitro and in vivo. Moreover, untreated KRASG13D mutants showed fastest growth in mice but remained sensitive to anti-EGFR therapy. Together, introducing mutation-specific oncogene signaling in CRC organoids resembles clinical phenotypes and improves understanding of genotype-phenotype correlations.
Transforming growth factor-beta signaling via ALK1 and ALK5 regulates distinct functional pathways in vein graft intimal hyperplasia
Authors: Low EL , Schwartze JT , Kurkiewicz A , Pek M , Kelly DJ , Shaw AS , Thorikay M , McClure J , McBride M , Arias-Rivas S , Francis SE , Morrell NW , Delles C , Herzyk P , Havenga MJ , Nicklin SA , Ten Dijke P , Baker AH , Bradshaw AC 
Published: December 2019

AbstractRationaleTransforming growth factor-beta (TGFβ) is tightly regulated at multiple levels, with regulation at the receptor level now recognized as a key determinant of the cellular response to this pleiotropic cytokine. TGFβ promotes saphenous vein graft neointima formation after coronary artery bypass graft (CABG) surgery, inducing smooth muscle cell (SMC) hyperplasia and fibrosis by signaling via activin receptor-like kinase 5(ALK5). However, the role of the alternate TGFβ receptor ALK1 remains completely unknown.ObjectiveTo define the receptor pathways activated by TGFβ in SMCs and their mechanistic importance during CABG neointima formation.Methods and resultsRadioligand co-IP assays revealed direct interactions between TGFβ, ALK5 and ALK1 in primary saphenous vein graft SMC (HSVSMC) from patients undergoing CABG. Knockdown and pharmacological inhibition of ALK5 or ALK1 in HSVSMC significantly attenuated TGFβ-induced phosphorylation of receptor-regulated (R)-Smads 2/3 and 1/5, respectively. Microarray profiling followed by qRT-PCR validation showed that TGFβ induced distinct transcriptional networks downstream of ALK5 or ALK1, associated with HSVSMC contractility and migration, respectively and confirmed using migration assays as well as qRT-PCR and western blot assays of contractile SMC markers. scRNAseq analysis of TGFβ-treated HSVSMC identified distinct subgroups of cells showing ALK5 or ALK1 transcriptional responses, while RNA velocity analyses indicated divergence in differentiation towards ALK5 or ALK1-dominant lineages. ALK1, ALK5 and their downstream effectors pSmad1/5 and pSmad2/3 were localized to αSMA+ neointimal SMCs in remodelled mouse vein grafts. Pharmacological inhibition or genetic ablation of Smad1/5 substantially reducing neointima formation following acute vascular injury. Notably, expression and activation of ALK1, ALK5 and their respective downstream R-Smads was already evident in hyperplastic saphenous veins prior to grafting.ConclusionsWhilst canonical TGFβ signaling via ALK5 promotes a contractile HSVSMC phenotype, transactivation of ALK1 by TGFβ induces neointima formation by driving cell migration. Restoring the balance between ALK1 and ALK5 in HSVSMC may represent a novel therapeutic strategy for vein graft failure.
Assessing Environmental RNAi in a Non-Model Organism
Authors: Mondal Mosharrof , Peter Jacob , Scarbrough Obrie , Flynt Alex 
Published: December 2019

ABSTRACTRNA interference (RNAi) regulates gene expression in most multicellular organisms through binding of small RNA effectors to target transcripts. Exploiting this process is a popular strategy for genetic manipulation in invertebrates and has applications that includes control of pests. Successful RNAi technologies are dependent on delivery method. The most convenient method is likely feeding which is effective in some animals while others are insensitive. Thus, there is a need to develop RNAi technology on a per-species basis, which will require a comprehensive approach for assessing small RNA production from synthetic nucleic acids.Using a biochemical and sequencing approaches we investigated the metabolism of ingested RNAs using the two-spotted spider mite, Tetranychus urticae, as a model for RNAi insensitivity. This chelicerae arthropod shows only modest response to oral RNAi and has biogenesis pathways distinct from model organisms. To identify RNAi substrates in T. urticae we characterized processing of synthetic RNAs and those derived from plant transcripts ingested during feeding. Through characterization of read size length and overlaps of small RNA reads, visualization methods were developed that facilitate distinguish trans-acting small RNAs from degradation fragments.Using a strategy that delineates small RNA classes, we found a variety of RNA species are gated into spider mite RNAi pathways, however, potential mature trans-acting RNAs appear very unstable and rare. This suggests spider mite RNAi pathway products that originate as ingested materials may be preferentially metabolized instead of converted into regulators of gene expression. Spider mites infest a variety of plants, and it would be maladaptive to generate diverse gene regulators from dietary RNAs. This study provides a framework for assessing RNAi technology in organisms where genetic and biochemical tools are absent and benefit rationale design of RNAi triggers.
Genetic diversity and population structure of the endangered endemic speciesPaeonia decompositafrom China and implications for its conservation
Authors: Wang Shi-Quan 
Published: December 2019

AbstractPaeonia decomposita, endemic to China, has important ornamental, medicinal and economic value and is regarded as a threatened endangered plant. The genetic diversity and structure have seldom been described. A conservation management plan is not currently available. In present study, 16 pairs of SSR primers were used to evaluate genetic diversity and population structure. A total of 122 alleles were obtained with a mean of 7.625 alleles per locus. The expected heterozygosity (He) varied from 0.043 to 0.901 (mean 0.492). Moderate genetic diversity (He=0.405) among populations were revealed, with Danba identified as the center of genetic diversity. Mantel tests revealed a significant positive correlation between geographic and genetic distance among populations (r=0.592, P=0.0001), demonstrating consistency with the isolation by distance model. Analysis of molecular variance (AMOVA) results indicated that the principal genetic variation existed within populations (73.48%) rather than among populations (26.52%). Bayesian structure analysis and principal coordinate analysis (PCoA) supported classification of the populations into three clusters. Based on the level of observed genetic diversity, three management unints were proposed as conservation measures. The results will be beneficial for the conservation and exploitation of the species, providing a theoretical basis for further research on its evolution and phylogeography.HightlightsGenetic diversity among populations was moderate inPaeonia decompositaThere is significant positive correlation between geographic and genetic distance among populations, consistent with the isolation by distance modelPrincipal genetic variation existed within populations rather than among populations.The populations divided into three clusters.Three management unints were proposed as conservation measures.
Coding of odour and space in the hemimetabolous insect Periplaneta americana
Authors: Paoli Marco , Nishino Hiroshi , Couzin-Fuchs Einat , Giovanni Galizia C. 
Published: December 2019

AbstractThe general architecture of the olfactory system is highly conserved from insects to humans, but neuroanatomical and physiological differences can be observed across species. The American cockroach, inhabiting dark shelters with a rather stable olfactory landscape, is equipped with long antennae used for sampling the surrounding air-space for orientation and navigation. The antennae’s exceptional length provides a wide spatial working range for odour detection; however, it is still largely unknown whether and how this is also used for mapping the structure of the olfactory environment. By selective labelling antennal lobe projection neurons with a calcium sensitive dye, we investigated the logic of olfactory coding in this hemimetabolous insect. We show that odour responses are stimulus-specific and concentration-dependent, and that structurally related odorants evoke physiologically similar responses. By using spatially confined stimuli, we show that proximal stimulations induce stronger and faster responses than distal ones. Spatially confined stimuli of the female pheromone periplanone-B activate sub-region of the male macroglomerulus. Thus, we report that the combinatorial logic of odour coding deduced from holometabolous insects applies also to this hemimetabolous species. Furthermore, a fast decrease in sensitivity along the antenna, not supported by a proportionate decrease in sensillar density, suggests a neural architecture that strongly emphasizes neuronal inputs from the proximal portion of the antenna.Summary statementBy selective labelling the cockroach’s antennal lobe output neurons, we investigated the logic of olfactory coding in a hemimetabolous insect, showing that odour responses are stimulus-specific, concentration-dependent, and preserve information on the spatial structure of the stimulus.
On stability for learning human control strategy by demonstrations using SVM
Authors: Wang Zhiyang , Ou Yongsheng 
Published: December 2019

Purpose
This paper aims to deal with the trade-off of the stability and the accuracy in learning human control strategy from demonstrations. With the stability conditions and the estimated stability region, this paper aims to conveniently get rid of the unstable controller or controller with relatively small stability region. With this evaluation, the learning human strategy controller becomes much more robust to perturbations.

Design/methodology/approach
In this paper, the criterion to verify the stability and a method to estimate the domain of attraction are provided for the learning controllers trained with support vector machines (SVMs). Conditions are formulated based on the discrete-time system Lyapunov theory to ensure that a closed-form of the learning control system is strongly stable under perturbations (SSUP). Then a Chebychev point based approach is proposed to estimate its domain of attraction.

Findings
Some of such learning controllers have been implemented in the vertical balance control of a dynamically stable, statically unstable wheel mobile robot.