bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sulforaphane modulates microRNA expression in colon cancer cells to implicate the regulation of oncogenes CDC25A, HMGA2 and MYC
Authors: Dacosta Christopher A. , Paicu Claudia , Mohorianu Irina , Wang Wei , Xu Ping , Dalmay Tamas , Bao Yongping 
Published: September 2017

AbstractColorectal cancer is an increasingly important cause of morbidity and mortality, whose incidence is associated with dietary and lifestyle factors, particularly inversely so with the consumption of cruciferous vegetables. These vegetables contain glucosinolates, from the breakdown of which are derived isothiocyanates, such as sulforaphane. Sulforaphane is well-characterised for wide-ranging tumour-suppressive and chemoprotective activitiesin vitro, yet deeper elucidation of its biological interactions would aid in better realising its potential in chemoprevention and/or chemotherapy. There is evidence to suggest that sulforaphane modulates microRNA expression in the colon, thus implying the potential for microRNA modulation to play a role in the anti-cancer effects of sulforaphane. Therefore, the effects of sulforaphane on microRNA expression profiles in the colonic adenocarcinoma Caco-2 and non-cancerous colonic CCD-841 cell lines were investigated by small RNA cloning and deep sequencing, followed by Northern Blot validation experiments. Sulforaphane upregulated let-7f-5p and let-7g-5p expression at 24 h in Caco-2 cells, but not in CCD-841. Such treatment also downregulated miR-29b-3p in Caco-2. Dual luciferase assays with a let-7f-5p mimic and inhibitor confirmed the binding of the miRNA to predicted binding sites in the mRNA transcript 3’-UTRs of cell division cycle 25A (CDC25A), high-mobility group AT-hook-2 (HMGA2) and MYC. Therefore, we hypothesize that let-7f-5p translationally represses CDC25A, HMGA2 and MYC, thereby playing a role in the tumour-suppressive effects of sulforaphane. The apparent selectivity of let-7f-5p induction towards tumour cells would be therapeutically desirable if applicablein vivo. MiR-29b-3p is predicted to target a number of tumour-suppressing genes, further investigation of which could be informative regarding the potential of sulforaphane to suppress tumour progression.
Brain structure mediates the association between height and cognitive ability
Authors: Vuoksimaa Eero , Panizzon Matthew S. , Franz Carol E. , Fennema-Notestine Christine , Hagler Donald J. , Lyons Michael J. , Dale Anders M. , Kremen William S. 
Published: September 2017

AbstractHeight and general cognitive ability (GCA) are positively associated, but the underlying mechanisms of this relationship are unclear. We used a sample of 515 middle-aged male twins with structural magnetic resonance imaging data to study if the association between height and cognitive ability is mediated by cortical size. We used genetically, ontogenetically and phylogenetically distinct cortical metrics of cortical surface area (SA) and cortical thickness (CT). Our results indicate that the well-replicated height-GCA association is accounted for by individual differences in total cortical SA (highly heritable metric related to global brain size), and not mean CT, and that the genetic association between SA and GCA underlies the phenotypic height-GCA relationship.
Parsing the roles of neck-linker docking and tethered head diffusion in the stepping dynamics of kinesin
Authors: Zhang Zhechun , Goldtzvik Yonathan , Thirumalai D. 
Published: September 2017

Kinesin walks processively on microtubules (MTs) in an asymmetric hand-over-hand manner consuming one ATP molecule per 16 nm step. The contributions due to docking of the approximately thirteen residue neck linker to the leading head (deemed to be the power stroke), and diffusion of the trailing head contribute in propelling the motor by 16 nm have not been quantified. We use molecular simulations by creating a new coarse-grained model of the microtubule-kinesin complex, which reproduces the measured stall force as well as the force required to dislodge the motor head from the MT, to show that nearly three quarters of the step occurs by bidirectional stochastic motion of the TH. However, docking of the neck linker to the leading head constrains the extent of diffusion and minimizes the probability that kinesin takes side steps implying that both the events are necessary in the motility of kinesin, and for the maintenance of processivity. Surprisingly, we find that during a single step the trailing head stochastically hops multiple times between the geometrically accessible neighboring sites on the MT prior to forming a stable interaction with the target binding site with correct orientation between the motor head and theα/ßtubulin dimer.Significance StatementLike all motors, the stepping of the two headed conventional Kinesin on the microtubule is facilitated by conformational changes in the motor domain upon ATP binding and hydrolysis. Numerous experiments have revealed that docking of the thirteen residue neck linker (NL) to the motor domain of the leading plays a critical role in propelling the trailing head towards the plus end of the microtubule by nearly 16 nm in a single step. Surprisingly our molecular simulations reveal that nearly three quarters of the step occurs by stochastic diffusion of the trailing head. Docking of the NL restricts the extent of diffusion, thus forcing the motor to walk with overwhelming probability on a single protofilament of the MT.
Clustering and compositionality of task representations in a neural network trained to perform many cognitive tasks
Authors: Yang Guangyu Robert , Song H. Francis , Newsome William T. , Wang Xiao-Jing 
Published: September 2017

ABSTRACTA neural system has the ability to flexibly perform many tasks, but the underlying mechanism cannot be elucidated in traditional experimental and modeling studies designed for one task at a time. Here, we trained a single network model to perform 20 cognitive tasks that may involve working memory, decision-making, categorization and inhibitory control. We found that after training, recurrent units developed into clusters that are functionally specialized for various cognitive processes. We introduce a measure to quantify relationships between single-unit neural representations of tasks, and report five distinct types of such relationships that can be tested experimentally. Surprisingly, our network developed compositionality of task representations, a critical feature for cognitive flexibility, whereby one task can be performed by recombining instructions for other tasks. Finally, we demonstrate how the network could learn multiple tasks sequentially. This work provides a computational platform to investigate neural representations of many cognitive tasks.
Nutrient stoichiometry shapes microbial coevolution
Authors: Larsen Megan L. , Wilhelm Steven W. , Lennon Jay T. 
Published: September 2017

ABSTRACTCoevolution is a force contributing to the generation and maintenance of biodiversity. It is influenced by environmental conditions including the scarcity of essential resources, which can drive the evolution of defense and virulence traits. We conducted a long-term chemostat experiment where the marine cyanobacteriumSynechococcuswas challenged with a lytic phage under nitrogen (N) or phosphorus (P) limitation. This manipulation of nutrient stoichiometry altered the stability of host-parasite interactions and the underlying mode of coevolution. By assessing infectivity with >18,000 pairwise challenges, we documented directional selection for increased phage resistance, consistent with arms-race dynamics while phage infectivity fluctuated through time, as expected when coevolution is driven by negative frequency-dependent selection. The resulting infection networks were 50 % less modular under N-versus P-limitation reflecting host-range contraction and asymmetric coevolutionary trajectories. Nutrient stoichiometry affects eco-evolutionary feedbacks in ways that may alter the dynamics and functioning of environmental and host-associated microbial communities.
Monetary feedback modulates performance and electrophysiological indices of belief updating in reward learning
Authors: Bennett Daniel , Sasmita Karen , Maloney Ryan T. , Murawski Carsten , Bode Stefan 
Published: September 2017

AbstractBelief updating entails the incorporation of new information about the environment into internal models of the world. Bayesian inference is the statistically optimal strategy for performing belief updating in the presence of uncertainty. An important open question is whether the use of cognitive strategies that implement Bayesian inference is dependent upon motivational state and, if so, how this is reflected in electrophysiological signatures of belief updating in the brain. Here we recorded the electroencephalogram of participants performing a simple reward learning task with both monetary and non-monetary instructive feedback conditions. Our aim was to distinguish the influence of the rewarding properties of feedback on belief updating from the information content of the feedback itself. A Bayesian updating model allowed us to quantify different aspects of belief updating across trials, including the size of belief updates and the uncertainty of beliefs. Faster learning rates were observed in the monetary feedback condition compared to the instructive feedback condition, while belief updates were generally larger, and belief uncertainty smaller, with monetary compared to instructive feedback. Larger amplitudes in the monetary feedback condition were found for three event-related potential components: the P3a, the feedback-related negativity (FRN) and the late positive potential (LPP). These findings suggest that motivational state influences inference strategies in reward learning, and this is reflected in the electrophysiological correlates of belief updating.
Chaperone AMPylation modulates aggregation and toxicity of neurodegenerative disease-associated polypeptides
Authors: Truttmann Matthias C. , Pincus David , Ploegh Hidde L. 
Published: September 2017

AbstractProteostasis is critical to maintain organismal viability, a process counteracted by aging-dependent protein aggregation. Chaperones of the heat shock protein (HSP) family help control proteostasis by reducing the burden of unfolded proteins. They also oversee the formation of protein aggregates. Here, we explore how AMPylation – a post-translational protein modification that has emerged as a powerful modulator of HSP70 activity – influences the dynamics of protein aggregation. We find that adjustments of cellular AMPylation levels inC.elegansdirectly affect aggregation properties and associated toxicity of amyloid-β (Aβ), of a polyglutamine (polyQ)- extended polypeptide and of α-synuclein (α-syn). Expression of a constitutively activeC. elegansAMPylase Fic-1(E274G) under its own promoter expedites aggregation of Aβ and α-syn, and drastically reduces their toxicity. A deficiency in AMPylation decreases the cellular tolerance for aggregation-prone polyQ proteins and alters their aggregation behavior. Over-expression of Fic-1(E274G) interferes with cell survival and larval development, underscoring the need for tight control of AMPylase activityin vivo. We thus define a link between HSP70 AMPylation and the dynamics of protein aggregation in neurodegenerative disease models. Our results are consistent with a cyto-protective, rather than a cytotoxic role for such protein aggregates.
Layered structure and complex mechanochemistry of a strong bacterial adhesive
Authors: Hernando-Pérez Mercedes , Setayeshgar Sima , Hou Yifeng , Temam Roger , Brun Yves V , Dragnea Bogdan , Berne Cécile 
Published: September 2017

AbstractWhile designing adhesives that perform in aqueous environments has proven challenging for synthetic adhesives, microorganisms commonly produce bioadhesives that efficiently attach to a variety of substrates, including wet surfaces that remain a challenge for industrial adhesives. The aquatic bacteriumCaulobacter crescentususes a discrete polar polysaccharide complex, the holdfast, to strongly attach to surfaces and resist flow. The holdfast is extremely versatile and has an impressive adhesive strength. Here, we use atomic force microscopy (AFM) to unravel the complex structure of the holdfast and characterize its chemical constituents and their role in adhesion. We used purified holdfasts to dissect the intrinsic properties of this component as a biomaterial, without the effect of the bacterial cell body. Our data support a model where the holdfast is a heterogeneous material composed of two layers: a stiff nanoscopic core, covered by a sparse, flexible brush layer. These two layers contain not onlyN-acetyl-D-glucosamine (NAG), the only yet identified component present in the holdfast, but also peptides and DNA, which provide structure and adhesive character. Biochemical experiments suggest that, while polypeptides are the most important components for adhesive force, the presence of DNA mainly impacts the brush layer and initial adhesion, and NAG plays a primarily structural role within the core. Moreover, our results suggest that holdfast matures structurally, becoming more homogeneous over time. The unanticipated complexity of both the structure and composition of the holdfast likely underlies its distinctive strength as a wet adhesive and could inform the development of a versatile new family of adhesives.
Assessing actimeters for inclusion in the Healthy Brain Network
Authors: Clucas Jonathan , White Curt , Koo Bonhwang , Milham Michael , Klein Arno 
Published: September 2017

AbstractBackgroundThe Healthy Brain Network is an openly shared pediatric psychiatric biobank with a target of 10,000 participants between the ages of 5 and 21, inclusively In adding ecological actimetry to the Healthy Brain Network, we intend to use appropriate, accurate, reliable tools. Currently a wide range of personal activity trackers are commercially available, providing a wide variety of sensor configurations. For many of these devices, accelerometry provides the basis of measuring both physical activity and sleep with comparable derivative measures.ResultsIn order to include an ecological biotracker in the Healthy Brain Network protocol, we first evaluated the specifications of a variety of actimeters available for purchase. We then acquired physical instances of 5 of these devices (ActiGraph wGT3X-BT, Empatica Embrace, Empatica E4, GENEActiv Original, and Wavelet Wristband) and wore each of them in our daily lives, annotating our activities and evaluating the reasonableness of the data from each device and the logistical affordances of each device.ConclusionsWe decided that the ActiGraph wGT3X-BT is the most appropriate device for inclusion in the Healthy Brain Network. However, none of the devices we evaluated was clearly superior or inferior to the rest; rather, each device seems to have use cases in which that device excels beyond the others.
HT‐SuperSAGE of the gut tissue of a Vip3Aa‐resistant Heliothis virescens (Lepidoptera: Noctuidae) strain provides insights into the basis of resistance
Authors: Ayra‐Pardo Camilo , Ochagavía Maria E. , Raymond Ben , Gulzar Asim , Rodríguez‐Cabrera Lianet , Rodríguez de la Noval Claudia , Morán Bertot Ivis , Terauchi Ryohei , Yoshida Kentaro , Matsumura Hideo , Téllez Rodríguez Pilar , Hernández Hernández Daily , Borrás‐Hidalgo Orlando , Wright Denis J. 
Published: September 2017

AbstractMultitoxin Bt‐crops expressing insecticidal toxins with different modes of action, for example, Cry and Vip, are expected to improve resistance management in target pests. While Cry1A resistance has been relatively well characterized in some insect species, this is not the case for Vip3A, for which no mechanism of resistance has yet been identified. Here we applied HT‐SuperSAGE to analyze the transcriptome of the gut tissue of tobacco budworm Heliothis virescens (F.) laboratory‐selected for Vip3Aa resistance. From a total of 1 324 252 sequence reads, 5 895 126‐bp tags were obtained representing 17 751 nonsingleton unique transcripts (UniTags) from genetically similar Vip3Aa‐resistant (Vip–Sel) and susceptible control (Vip–Unsel) strains. Differential expression was significant (≥2.5 fold or ≤0.4; P < 0.05) for 1989 sequences (11.2% of total UniTags), where 420 represented overexpressed (OE) and 1569 underexpressed (UE) genes in Vip–Sel. BLASTN searches mapped 419 UniTags to H. virescens sequence contigs, of which, 416 (106 OE and 310 UE) were unambiguously annotated to proteins in NCBI nonredundant protein databases. Gene Ontology distributed 345 of annotated UniTags in 14 functional categories with metabolism (including serine‐type hydrolases) and translation/ribosome biogenesis being the most prevalent. A UniTag homologous to a particular member of the REsponse to PAThogen (REPAT) family was found among most overexpressed, while UniTags related to the putative Vip3Aa‐binding ribosomal protein S2 (RpS2) were underexpressed. qRT‐PCR of a subset of UniTags validated the HT‐SuperSAGE data. This study is the first providing lepidopteran gut transcriptome associated with Vip3Aa resistance and a foundation for future attempts to elucidate the resistance mechanism.
DNA barcoding of invasive plants in China: A resource for identifying invasive plants
Authors: Xu Song‐Zhi , Li Zhen‐Yu , Jin Xiao‐Hua 
Published: September 2017

AbstractInvasive plants have aroused attention globally for causing ecological damage and having a negative impact on the economy and human health. However, it can be extremely challenging to rapidly and accurately identify invasive plants based on morphology because they are an assemblage of many different families and many plant materials lack sufficient diagnostic characteristics during border inspections. It is therefore urgent to evaluate candidate loci and build a reliable genetic library to prevent invasive plants from entering China. In this study, five common single markers (ITS, ITS2, matK, rbcL and trnH‐psbA) were evaluated using 634 species (including 469 invasive plant species in China, 10 new records to China, 16 potentially invasive plant species around the world but not introduced into China yet and 139 plant species native to China) based on three different methods. Our results indicated that ITS2 displayed largest intra‐ and interspecific divergence (1.72% and 91.46%). Based on NJ tree method, ITS2, ITS, matK, rbcL and trnH‐psbA provided 76.84%, 76.5%, 63.21%, 52.86% and 50.68% discrimination rates, respectively. The combination of ITS + matK performed best and provided 91.03% discriminatory power, followed by ITS2 + matK (85.78%). For identifying unknown individuals, ITS + matK had 100% correct identification rate based on our database, followed by ITS/ITS2 (both 93.33%) and ITS2 + matK (91.67%). Thus, we propose ITS/ITS2 + matK as the most suitable barcode for invasive plants in China. This study also demonstrated that DNA barcoding is an efficient tool for identifying invasive species.
Estimating species colonization dates using DNA in lake sediment
Authors: Olajos Fredrik , Bokma Folmer , Bartels Pia , Myrstener Erik , Rydberg Johan , Öhlund Gunnar , Bindler Richard , Wang Xiao‐Ru , Zale Rolf , Englund Göran 
Published: September 2017

Abstract

Detection of DNA in lake sediments holds promise as a tool to study processes like extinction, colonization, adaptation and evolutionary divergence. However, low concentrations make sediment DNA difficult to detect, leading to high false negative rates. Additionally, contamination could potentially lead to high false positive rates. Careful laboratory procedures can reduce false positive and negative rates, but should not be assumed to completely eliminate them. Therefore, methods are needed that identify potential false positive and negative results, and use this information to judge the plausibility of different interpretations of DNA data from natural archives.

We developed a Bayesian algorithm to infer the colonization history of a species using records of DNA from lake‐sediment cores, explicitly labelling some observations as false positive or false negative. We illustrate the method by analysing DNA of whitefish (Coregonus lavaretus L.) from sediment cores covering the past 10,000 years from two central Swedish lakes. We provide the algorithm as an R‐script, and the data from this study as example input files.

In one lake, Stora Lögdasjön, where connectivity with the proto‐Baltic Sea and the degree of whitefish ecotype differentiation suggested colonization immediately after deglaciation, DNA was indeed successfully recovered and amplified throughout the post‐glacial sediment. For this lake, we found no loss of detection probability over time, but a high false negative rate. In the other lake, Hotagen, where connectivity and ecotype differentiation suggested colonization long after deglaciation, DNA was amplified only in the upper part of the sediment, and colonization was estimated at 2,200 bp based on the assumption that successful amplicons represent whitefish presence. Here the earliest amplification represents a false positive with a posterior probability of 41%, which increases the uncertainty in the estimated time of colonization.

Complementing careful laboratory procedures aimed at preventing contamination, our method estimates contamination rates from the data. By combining these results with estimates of false negative rates, our models facilitate unbiased interpretation of data from natural DNA archives.
Prenatal Alcohol Exposure Leads to Enhanced Serine 9 Phosphorylation of Glycogen Synthase Kinase‐3β (GSK‐3β) in the Hippocampal Dentate Gyrus of Adult Mouse
Authors: Cunningham Lee Anna , Newville Jessie , Li Lu , Tapia Phillip , Allan Andrea M. , Valenzuela C. Fernando 
Published: September 2017

BackgroundThe goal of this study was to evaluate the expression and serine 9 phosphorylation of glycogen synthase kinase (GSK‐3β) within the adult hippocampal dentate gyrus (DG) in a preclinical mouse model of fetal alcohol spectrum disorders. GSK‐3β is a multifunctional kinase that modulates many hippocampal processes affected by gestational alcohol, including synaptic plasticity and adult neurogenesis. GSK‐3β is a constitutively active kinase that is negatively regulated by phosphorylation at the serine 9 residue.MethodsWe utilized a well‐characterized limited access “drinking‐in‐the‐dark” paradigm of prenatal alcohol exposure (PAE) and measured p(Ser9)GSK‐3β and total GSK‐3β within adult DG by Western blot analysis. In addition, we evaluated the expression pattern of both p(Ser9)GSK‐3β and total GSK‐3β within the adult hippocampal dentate of PAE and control mice using high‐resolution confocal microscopy.ResultsOur findings demonstrate a marked 2.0‐fold elevation of p(Ser9)GSK‐3β in PAE mice, concomitant with a more moderate 36% increase in total GSK‐3β. This resulted in an approximate 63% increase in the p(Ser9)GSK‐3β/GSK‐3β ratio. Immunostaining revealed robust GSK‐3β expression within Cornu Ammonis (CA) pyramidal neurons, hilar mossy cells, and a subset of GABAergic interneurons, with low levels of expression within hippocampal progenitors and dentate granule cells.ConclusionsThese findings suggest that PAE may lead to a long‐term disruption of GSK‐3β signaling within the DG, and implicate mossy cells, GABAergic interneurons, and CA primary neurons as major targets of this dysregulation.