bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oxygen-sensing neurons reciprocally regulate peripheral lipid metabolism via neuropeptide signaling inCaenorhabditis elegans
Authors: Hussey Rosalind , Witham Emily , Vanstrum Erik , Mesgarzadeh Jaleh , Ratanpal Harkaranveer , Srinivasan Supriya 
Published: May 2017

AbstractThe mechanisms by which the sensory environment instructs metabolic homeostasis remains poorly understood. In this report, we show that oxygen, a potent environmental signal, is an important regulator of whole body lipid metabolism.C. elegansoxygen-sensing neurons reciprocally regulate peripheral lipid metabolism under normoxia in the following way: under high oxygen and food absence, URX sensory neurons are activated, and stimulate fat loss in the intestine, the major metabolic organ forC. elegans. Under lower oxygen conditions or when food is present, the BAG sensory neurons respond by repressing the resting properties of the URX neurons. A genetic screen to identify modulators of this effect led to the identification of a BAG-neuron-specific neuropeptide called FLP-17, whose cognate receptor EGL-6 functions in URX neurons. Thus, BAG sensory neurons counterbalance the metabolic effect of tonically active URX neurons via neuropeptide communication. The combined regulatory actions of these neurons serve to precisely tune the rate and extent of fat loss, to the availability of food and oxygen.
Transcription of Repeats Activates INterferon (TRAIN) in response to chromatin destabilization induced with anti-cancer small molecule
Authors: Leonova Katerina , Safina Alfiya , Nesher Elimelech , Sandlesh Poorva , Pratt Rachel , Burkhart Catherine , Lipchick Britney , Frangou Costakis , Koman Igor , Wang Jianmin , Kirsanov Kirill , Yakubovskaya Marianna G. , Gudkov Andrei V. , Gurova Katerina 
Published: May 2017

AbstractThe anticancer activity of genotoxic agents has been intensively studied, while the mechanisms of action of drugs destabilizing the epigenome are far less understood. We previously found that DNA hypomethylation in the absence of p53 leads to transcriptional desilencing of repetitive DNA elements, such as pericentromeric repeats and endogenous retroelements, which is associated with an interferon type I response, a phenomenon we named TRAIN (Transcription ofRepeatsActivatesINterferon). Here, we report that curaxin, a small molecule anticancer drug candidate, which destabilizes nucleosomes via disruption of histone/DNA interactions, can induce TRAIN independently of the p53 status of a cell. Furthermore, curaxin inhibits oncogene-induced transformation in an interferon-dependent manner, suggesting that cancer prevention by curaxin, previously attributed to its p53-activating and NF-kappaB-inhibiting activities, may also involve the induction of the interferon response to epigenetic derepression of the cellular “repeatome.” Moreover, we observed that another type of drugs decondensing chromatin, histone deacetylase inhibitor, also induces TRAIN. Thus, we proposed that TRAIN may be one of the mechanisms ensuring epigenetic integrity of cells via elimination of cells with desilenced chromatin.
Modality-independent coding of scene categories in prefrontal cortex
Authors: Jung Yaelan , Larsen Bart , Walther Dirk B. 
Published: May 2017

AbstractNatural environments convey information through multiple sensory modalities, all of which contribute to people’s percepts. Although it has been shown that visual or auditory content of scene categories can be decoded from brain activity, it remains unclear where and how humans integrate different sensory inputs and represent scene information beyond a specific sensory modality domain. To address this question, we investigated how categories of scene images and sounds are represented in several brain regions. A mixed gender group of healthy human subjects participated the present study, where their brain activity was measured with fMRI while viewing images or listening to sounds of different places. We found that both visual and auditory scene categories can be decoded not only from modality-specific areas, but also from several brain regions in the temporal, parietal, and prefrontal cortex. Intriguingly, only in the prefrontal cortex, but not in any other regions, categories of scene images and sounds appear to be represented in similar activation patterns, suggesting that scene representations in the prefrontal cortex are modality-independent. Furthermore, the error patterns of neural decoders indicate that category-specific neural activity patterns in the middle and superior frontal gyri are tightly linked to categorization behavior. Our findings demonstrate that complex scene information is represented at an abstract level in the prefrontal cortex, regardless of the sensory modality of the stimulus.Statement of SignificanceOur experience in daily life requires the integration of multiple sensory inputs such as images, sounds, or scents from the environment. Here, for the first time, we investigated where and how in the brain information about the natural environment from multiple senses is merged to form modality-independent representations of scene categories. We show direct decoding of scene categories across sensory modalities from patterns of neural activity in the prefrontal cortex. We also conclusively tie these neural representations to human categorization behavior based on the errors from the neural decoder and behavior. Our findings suggest that the prefrontal cortex is a central hub for integrating sensory information and computing modality-independent representations of scene categories.
Exploiting theZIP4homologue within the wheatPh1locus has identified two lines exhibiting homoeologous crossover in wheat-wild relative hybrids
Authors: Rey María-Dolores , Martín Azahara C , Higgins Janet , Swarbreck David , Uauy Cristobal , Shaw Peter , Moore Graham 
Published: May 2017

AbstractDespite possessing related ancestral genomes, hexaploid wheat behaves as a diploid during meiosis. The wheatPh1locus promotes accurate synapsis and crossover of homologous chromosomes. Interspecific hybrids between wheat and wild relatives are exploited by breeders to introgress important traits from wild relatives into wheat, although in hybrids between hexaploid wheat and wild relatives, which possess only homoeologues, crossovers do not take place during meiosis at metaphase I. However, in hybrids betweenPh1deletion mutants and wild relatives, crossovers do take place. A singlePh1deletion (ph1b) mutant has been exploited for the last 40 years for this activity. We show here that selection of chemical induced mutant lines possessing mutations inTaZIP4-B2exhibit high levels of homoeologous crossovers when crossed with a wild relative. Exploitation ofTazip4-B2mutants rather than mutants with wholePh1locus deletions may improve introgression of wild relative chromosome segments into wheat. Such mutant lines may be more stable over multiple generations, as multivalents causing accumulation of chromosome translocations are less frequent.Key messageExploiting theZIP4homologue within the wheatPh1locus has identified two wheat mutants through a non-GM route, which can be exploited as an alternative to the Chinese Springph1bmutant in wheat introgression strategies.
Specific Virus-Host Genome Interactions Revealed by Tethered Chromosome Conformation Capture
Authors: Li Haochen , Kalhor Reza , Li Bing , Su Trent , Berk Arnold J. , Kurdistani Siavash K. , Alber Frank , Chen Lin 
Published: May 2017

AbstractViruses have evolved a variety of mechanisms to interact with host cells for their adaptive benefits, including subverting host immune responses and hijacking host DNA replication/transcription machineries [1–3]. Although interactions between viral and host proteins have been studied extensively, little is known about how the vial genome may interact with the host genome and how such interactions could affect the activities of both the virus and the host cell. Since the three-dimensional organization of a genome can have significant impact on genomic activities such as transcription and replication, we hypothesize that such structure-based regulation of genomic functions also applies to viral genomes depending on their association with host genomic regions and their spatial locations inside the nucleus. Here, we used Tethered Chromosome Conformation Capture (TCC) to investigate viral-host genome interactions between the adenovirus and human lung fibroblast cells. We found viral-host genome interactions were enriched in certain active chromatin regions and chromatin domains marked by H3K27me3. The contacts by viral DNA seems to impact the structure and function of the host genome, leading to remodeling of the fibroblast epigenome. Our study represents the first comprehensive analysis of viral-host interactions at the genome structure level, revealing unexpectedly specific virus-host genome interactions. The non-random nature of such interactions indicates a deliberate but poorly understood mechanism for targeting of host DNA by foreign genomes.
MutS-Homolog2silencing generates tetraploid meiocytes in tomato (Solanum lycopersicum)
Authors: Sarma Supriya , Pandey Arun Kumar , Ravi Maruthachalam , Sreelakshmi Yellamaraju , Sharma Rameshwar 
Published: May 2017

SUMMARYMSH2 is the core protein of MutS-homolog family involved in recognition and repair of the errors in the DNA. While other members of MutS-homolog family reportedly regulate mitochondrial stability, meiosis, and fertility, MSH2 is believed to participate mainly in mismatch repair. The search for polymorphism inMSH2sequence in tomato accessions revealed both synonymous and nonsynonymous SNPs; however, SIFT algorithm predicted that none of the SNPs influenced MSH2 protein function. The silencing ofMSH2gene expression by RNAi led to phenotypic abnormalities in highly-silenced lines, particularly in the stamens with highly reduced pollen formation.MSH2silencing exacerbated formation of UV-B induced thymine dimers and blocked light-induced repair of the dimers. TheMSH2silencing also affected the progression of male meiosis to a varying degree with either halt of meiosis at zygotene stage or formation of diploid tetrads. The immunostaining of male meiocytes with centromere localized CENPC (Centromere protein C) protein antibody showed the presence of 48 univalent along with 24 bivalent chromosomes suggesting abnormal tetraploid meiosis. The mitotic cells of root tips of silenced lines showed diploid nuclei but lacked intervening cell plates leading to cells with syncytial nuclei. Thus we speculate that tetraploid pollen mother cells may have arisen due to the fusion of syncytial nuclei before the onset of meiosis. It is likely that in addition to Mismatch repair (MMR), MSH2 may have an additional role in regulating ploidy stability.
RANKL signaling sustains primary tumor growth in genetically engineered mouse models of lung adenocarcinoma
Authors: Faget Julien , Contat Caroline , Zangger Nadine , Peters Solange , Meylan Etienne 
Published: May 2017

SummaryHypothesisNon-small cell lung cancer (NSCLC) is the leading cause of cancer mortality. Recent retrospective clinical analyses suggest that blocking the receptor activator of NF-κB (RANK) signaling pathway inhibits the growth of NSCLC and might represent a new treatment strategy.MethodsRANKandRANKLexpression in human lung adenocarcinoma was interrogated from publicly available gene expression datasets. Several genetically engineered mouse models were used to evaluate treatment efficacy of RANK-Fc to block RANKL, with primary tumor growth measured longitudinally using micro-computed tomography. A combination of RANKL blockade with cisplatin was tested to mirror an ongoing clinical trial.ResultsIn human lung adenocarcinoma datasets,RANKLexpression was associated with decreased survival andKRASmutation, with the highest levels in tumors with co-occurringKRASandLKB1mutations. InKrasLSL-G12D/WT, KrasLSL-G12D/WT;Lkb1Flox/FloxandKrasLSL-G12D/WT;p53Flox/Floxmouse models of lung adenocarcinoma, we monitored an impaired progression of tumors upon RANKL blockade. Despite elevated expression of RANKL and RANK in immune cells, treatment response was not associated with major changes in the tumor immune microenvironment. Combined RANK-Fc with cisplatin revealed increased efficacy compared to single agents.ConclusionsRANKL blocking agents impair the growth of primary lung tumors in several mouse models of lung adenocarcinoma, and suggest that patients withKRASmutant lung tumors will benefit from such treatments.
Postmitotic separation enables selective niche retention of one daughter cell in intestinal crypts and is facilitated by interkinetic nuclear migration and basal tethering
Authors: Carroll Thomas D. , Langlands Alistair J. , Osborne James M. , Newton Ian P. , Appleton Paul L. , Näthke Inke 
Published: May 2017

AbstractHomeostasis of renewing tissues requires balanced proliferation, differentiation and movement. This is particullary important in the intestinal epithelium where lineage tracing suggests that stochastic differentiation choices are intricately coupled to position. To determine how position is achieved we followed proliferating cells in intestinal organoids and discovered that behaviour of mitotic sisters predicted long-term positioning. Normally, 70% of sisters remain neighbours while 30% lose contact separating after cytokinesis. Postmitotic placements predict differences in positions of sisters later: adjacent sisters reach similar positions; one separating sister remains close to its birthplace, the other moves upward. Computationally modelling crypt dynamics confirmed post-mitotic separation as a mechanism for placement of sisters into different niches. Separation depends on interkinetic nuclear migration, cell size, and asymmetric tethering by a basal process. These processes are altered whenAdenomatous polyposis coli(Apc) is mutant and separation is lost. We conclude that post-mitotic placement enables stochastic niche exit and when defective, supports the clonal expansion ofApcmutant cells.
A face identity hallucination (palinopsia) generated by intracerebral stimulation of the face-selective right lateral fusiform cortex
Authors: Jonas Jacques , Brissart Hélène , Hossu Gabriela , Colnat-Coulbois Sophie , Vignal Jean-Pierre , Rossion Bruno , Maillard Louis 
Published: May 2017

AbstractWe report the case of a patient (MB, young female human subject) who systematically experiences confusion between perceived facial identities when electrically stimulated inside the lateral section of the right fusiform gyrus. In the presence of a face stimulus (an experimenter or a photograph), intracerebral electrical stimulation in this region generates a perceptual hallucination of an individual facial part integrated within the whole perceived face, i.e. facial palinopsia. In the presence of a distracting stimulus (visual scene or object picture), the patient also experiences an individual face percept superimposed on the non-face stimulus. The stimulation site evoking this category-selective transient palinopsia is localized in a region showing highly selective responses to faces both with functional magnetic resonance imaging (“Fusiform Face Area”, “FFA”) and intracerebral electrophysiological recordings during fast periodic visual stimulation (FPVS). Importantly, the largest electrophysiological response to fast periodic changes of facial identity is also found at this location. Altogether, these observations suggest that a local face-selective region of the right lateral fusiform gyrus suffices to generate a vivid percept of an individual face, supporting the active role of this region in individual face representation.
A reagentless biosensor for mRNA: a new tool to study transcription
Authors: Cook Alexander , Hari-Gupta Yukti , Toseland Christopher P. 
Published: May 2017

ABSTRACTGene expression, catalysed by RNA polymerases, is one of the most fundamental processes in living cells. Yet, the means to study their activity are currently limited. The majority of methods to quantify mRNA are based upon initial purification of the nucleic acid. This leads to experimental inaccuracies and loss of product. Here, we describe the use of a reagentless mRNA fluorescent biosensor based upon the single stranded binding (SSB) protein. In this study, SSB showed similar binding properties to mRNA, to that of its native substrate, ssDNA. Furthermore, fluorescently labelled MDCC-SSB gave the same fluorescence response with both ssDNA and ssRNA, in a concentration dependent manner. When directly compared to RT-qPCR, we found the biosensor to be more reproducible with no product lost through purification. Therefore, the MDCC-SSB is a novel tool for comparative measurement of mRNA yield followingin vitrotranscription.
Analysis and correction of compositional bias in sparse sequencing count data
Authors: Kumar M. Senthil , Slud Eric V. , Okrah Kwame , Hicks Stephanie C. , Hannenhalli Sridhar , Bravo Héctor Corrada 
Published: May 2017

AbstractCount data derived from high-throughput DNA sequencing is frequently used in quantitative molecular assays. Due to properties inherent to the sequencing process, unnormalized count data is compositional, measuring relative and not absolute abundances of the assayed features. This compositional bias confounds inference of absolute abundances. We demonstrate that existing techniques for estimating compositional bias fail with sparse metagenomic 16S count data and propose an empirical Bayes normalization approach to overcome this problem. In addition, we clarify the assumptions underlying frequently used scaling normalization methods in light of compositional bias, including scaling methods that were not designed directly to address it.
Sleep Benefits Memory for Semantic Category Structure While Preserving Exemplar-Specific Information
Authors: Schapiro Anna C. , McDevitt Elizabeth A. , Chen Lang , Norman Kenneth A. , Mednick Sara C. , Rogers Timothy T. 
Published: May 2017

AbstractSemantic memory encompasses knowledge about both the properties that typify concepts (e.g. robins, like all birds, have wings) as well as the properties that individuate conceptually related items (e.g. robins, in particular, have red breasts). We investigate the impact of sleep on new semantic learning using a property inference task in which both kinds of information are initially acquired equally well. Participants learned about three categories of novel objects possessing some properties that were shared among category exemplars and others that were unique to an exemplar, with exposure frequency varying across categories. In Experiment 1, memory for shared properties improved and memory for unique properties was preserved across a night of sleep, while memory for both feature types declined over a day awake. In Experiment 2, memory for shared properties improved across a nap, but only for the lower-frequency category, suggesting a prioritization of weakly learned information early in a sleep period. The increase was significantly correlated with amount of REM, but was also observed in participants who did not enter REM, suggesting involvement of both sleep stages. The results provide the first evidence that sleep improves memory for the shared structure of object categories, while simultaneously preserving object-unique information.
Two Novel Bioactive Peptides from Antarctic Krill with Dual Angiotensin Converting Enzyme and Dipeptidyl Peptidase IV Inhibitory Activities
Authors: Ji Wei , Zhang Chaohua , Ji Hongwu 
Published: May 2017

AbstractInhibition of dipeptidyl peptidase IV (DPP‐IV) and angiotensin converting enzyme (ACE) are considered useful in managing 2 often associated conditions: diabetes and hypertension. In this study, corolase PP was used to hydrolyze Antarctic krill protein. The hydrolysate (AKH) was isolated by ultrafiltration and purified by size‐exclusion chromatography, ion exchange chromatography and reversed‐phase high‐performance liquid chromatography (RP‐HPLC) sequentially. The in vitro inhibitory activities of all AKHs and several fractions obtained against ACE and DPP‐IV were assessed. Two peptides, purified with dual‐strength inhibitory activity against ACE and DPP‐IV, were identified by TOF‐MS/MS. Results indicated that not all fractions exhibited dual inhibitory activities of ACE and DPP‐IV. The purified peptide Lys‐Val‐Glu‐Pro‐Leu‐Pro had half‐maximal inhibitory concentrations (IC50) of 0.93±0.05 and 0.73±0.04 mg/mL against ACE and DPP‐IV, respectively. The other peptide Pro‐Ala‐Leu had IC50 values of 0.64±0.05 and 0.88±0.03 mg/mL against ACE and DPP‐IV, respectively. This study firstly reported the sequences of dual bioactive peptides from Antarctic krill proteins, further provided new insights into the bioactive peptides responsible for the ACE and DPP‐IV inhibitory activities from the Antarctic krill protein hydrolysate to manage hypertension and diabetes.
Inhibitor‐Assisted High‐Pressure Inactivation of Bacteria in Skim Milk
Authors: Liu Hai‐bin , Li Ping , Sun Chang , Du Xin‐jun , Zhang Yan , Wang Shuo 
Published: May 2017

AbstractThe combined inactivation effects of high hydrostatic pressure (HHP) and antimicrobial compounds (potassium sorbate and ε‐polylysine [ε‐PL]) on 4 different bacterial strains present in skim milk and the effect of these treatments on milk quality were investigated in this study. HHP treatment at 500 MPa for 5 min reduced the populations of Escherichia coli, Salmonella enterica Typhimurium, Listeria monocytogenes, and Staphylococcus aureus from 6.5 log colony‐forming units (CFUs) or higher to less than 1 log CFU/mL. Compared to HHP alone, HHP with potassium or ε‐PL resulted in significantly higher reductions in the bacterial counts. After 5 min of treatment with HHP (500 MPa) and ε‐PL (2 mg/mL), no growth of E. coli, S. enterica Typhimurium, or L. monocytogenes in skim milk was observed during 15 d of refrigerated storage (4 ± 1 °C). Scanning electron microscopy analysis revealed that the synergistic treatments caused more serious damage to the bacterial cell walls. Quality assessments of the treated samples indicated that the combined treatments did not influence the color, the turbidity, the concentrations of –SH group of the proteins, or the in vitro digestion patterns of the milk. This study demonstrates that HHP with potassium or ε‐PL may be useful in the processing of milk or milk‐containing foods.
The Influence of pH and Sodium Hydroxide Exposure Time on Glucosamine and Acrylamide Levels in California‐Style Black Ripe Olives
Authors: Charoenprasert Suthawan , Zweigenbaum Jerry A. , Zhang Gong , Mitchell Alyson E. 
Published: May 2017

AbstractAcrylic acid, N‐acetyl‐glucosamine and glucosamine were investigated for their role in the formation of acrylamide in California‐style black ripe olives [CBROs]. Levels of acrylic acid and glucosamine are reported for the first time in fresh (333.50 ± 21.88 and 243.59 ± 10.06 nmol/g, respectively) and in brine‐stored olives (184.50 ± 6.02 and 165.88 ± 11.51 nmol/g, respectively). Acrylamide levels significantly increased when acrylic acid (35.2%), N‐acetyl‐glucosamine (29.9%), and glucosamine (124.0%) were added to olives prior to sterilization. However, isotope studies indicate these compounds do not contribute carbon and/or nitrogen atoms to acrylamide. The base‐catalyzed degradation of glucosamine is demonstrated in olive pulp and a strong correlation (r2 = 0.9513) between glucosamine in olives before sterilization and acrylamide formed in processed CBROs is observed. Treatment with sodium hydroxide (pH > 12) significantly reduces acrylamide levels over 1 to 5 d without impacting olive fruit texture.