bluuebunny/crossref_metadata_2025_split huggingface dataset:
Meta-analytic activation maps can help identify affective processes captured by contrast-based task fMRI: the case of threat-related facial expressions
Authors: Kim M. Justin , Knodt Annchen R. , Hariri Ahmad R. 
Published: October 2019

AbstractMeta-analysis of functional magnetic resonance imaging (fMRI) data is an effective method for capturing the distributed patterns of brain activity supporting discrete cognitive and affective processes. One opportunity presented by the resulting meta-analysis maps (MAMs) is as a reference for better understanding the nature of individual contrast maps (ICMs) derived from specific task fMRI data. Here, we compared MAMs from 148 neuroimaging studies representing the broad emotion categories of fear, anger, disgust, happiness, and sadness with ICMs from fearful > neutral and angry > neutral facial expressions from an independent dataset of task fMRI (n = 1263). Analyses revealed that both fear and anger ICMs exhibited the greatest pattern similarity to fear MAMs. As the number of voxels included for the computation of pattern similarity became more selective, the specificity of MAM-ICM correspondence decreased. Notably, amygdala activity long considered critical for processing threat-related facial expressions was neither sufficient nor necessary for detecting MAM-ICM pattern similarity effects. Our analyses suggest that both fearful and angry facial expressions are best captured by distributed patterns of brain activity associated with fear. More generally, our analyses demonstrate how MAMs can be leveraged to better understand affective processes captured by ICMs in task fMRI data.
The genome of the butternut canker pathogen, Ophiognomonia clavigignenti-juglandacearum shows an elevated number of genes associated with secondary metabolism and protection from host resistance responses in comparison with other members of the Diaporthales
Authors: Wu Guangxi , Schuelke Taruna A. , Broders Kirk 
Published: October 2019

AbstractOphiognomonia clavigignentijuglandacearum (Oc-j) is a plant pathogenic fungus that causes canker and branch dieback diseases in the hardwood tree butternut, Juglans cinerea. Oc-j is a member of the order of Diaporthales, which includes many other plant pathogenic species, several of which also infect hardwood tree species. In this study, we sequenced the genome of Oc-j and achieved a high-quality assembly and delineated the phylogeny of Oc-j within the Diaporthales order using a genome-wide multi-gene approach. We also further examined multiple gene families that might be involved in plant pathogenicity and degradation of complex biomass, which are relevant to a pathogenic life-style in a tree host. We found that the Oc-j genome contains a greater number of genes in these gene families compared to other species in Diaporthales. These gene families include secreted CAZymes, kinases, cytochrome P450, efflux pumps, and secondary metabolism gene clusters. The large numbers of these genes provide Oc-j with an arsenal to cope with the specific ecological niche as a pathogen of the butternut tree.
Subthreshold psychosis symptoms associated with molecular genetic risk in a population-based cohort: Findings from Generation Scotland
Authors: Docherty A.R. , Shabalin Andrey A. , Adkins Daniel E. , Mann Frank , Krueger Robert F. , Campbell Archie , Hayward Caroline , Porteous David J. , McIntosh Andrew M. , Kendler Kenneth S. 
Published: October 2019

AbstractImportanceSubthreshold psychosis symptoms in the general population may be associated with genetic risk for schizophrenia. In this analysis, empirically-derived symptom factor scores led to a detection of significant and robust polygenic signal.ObjectiveThis study sought to optimize genetic association with data-driven symptom factor scores, accounting for cohort factor structure and sex differences.DesignEFA-derived symptom factor scores were regressed onto PRS for schizophrenia in models accounting for age and genetic ancestry principal components. Follow-up examination of symptom factor score associations with other related genetic risks included ADHD, autism, bipolar disorder, major depression, and neuroticism.ParticipantsThis study examined the newly expanded symptom dataset from the Northern European ancestry cohort, Generation Scotland: Scottish Family Health Study (N = 9,105 individuals 18-65 years of age) comprising common variant and subthreshold psychosis symptom data. A total of 5,391 females and 3,713 males with age M[SD] = 45.2 [13] were included in the final analyses.Main Outcome and MeasureSubthreshold psychosis symptoms were measured using the Schizotypal Personality Questionnaire-Brief (SPQ-B). Primary phenotypic factor scores and genome-wide polygenic risk scores (PRS) reflected weighted sum scores and were examined as continuous measures. Polygenic risk scores were calculated from genome-wide association summary statistics using 7,358,674 imputed common genetic variants passing quality control.ResultsIn males, symptom factor scores were positively associated with polygenic risk for schizophrenia alone and implicated primarily interpersonal/negative symptoms. In females, symptom factor scores were positively associated with polygenic risks for ADHD and autism but not schizophrenia. Scores were robustly associated with genetic risk for neuroticism across both males and females.Conclusions and RelevanceThis study detected a significant association of subthreshold psychosis symptoms with genetic risk for schizophrenia and neuroticism in a population-based sample. Furthermore, important sex differences suggest a need for better understanding of schizophrenia risk assessment in females.Key PointsQuestionWhat molecular genetic risks are associated with subthreshold psychosis symptoms in the general population?FindingsIn a large population-based cohort (N = 9,084), significant associations of polygenic risks with symptoms were observed. Symptoms were associated with genetic risk for schizophrenia in males, for ADHD and autism spectrum disorder in females, and for neuroticism across both males and females.MeaningAssociations of genetic risk with symptoms in the general population are highly significant and suggest important sex differences.
Perceptual decisions about object shape bias visuomotor coordination during rapid interception movements
Authors: Barany Deborah A. , Gómez-Granados Ana , Schrayer Margaret , Cutts Sarah A. , Singh Tarkeshwar 
Published: October 2019

AbstractVisual processing in parietal areas of the dorsal stream facilitates sensorimotor transformations for rapid movement. This action-related visual processing is hypothesized to play a distinct functional role from the perception-related processing in the ventral stream. However, it is unclear how the two streams interact when perceptual identification is a prerequisite to executing an accurate movement. In the current study, we investigated how perceptual decision-making involving the ventral stream influences arm and eye movement strategies. Participants (N = 26) moved a robotic manipulandum using right whole-arm movements to rapidly reach a stationary object or intercept a moving object on an augmented-reality display. On some blocks of trials, participants needed to identify the shape of the object (circle or ellipse) as a cue to either hit the object (circle) or move to a pre-defined location away from the object (ellipse). We found that during perceptual decision-making, there was an increased urgency to act during interception movements relative to reaching, which was associated with more decision errors. Faster hand reaction times were correlated with a strategy to adjust the movement post-initiation, and this strategy was more prominent during interception. Saccadic reaction times were faster and initial gaze lags and gains greater during decisions, suggesting that eye movements adapt to perceptual demands for guiding limb movements. Together, our findings suggest that the integration of ventral stream information with visuomotor planning depends on imposed (or perceived) task demands.New and NoteworthyVisual processing for perception and for action are thought to be mediated by two specialized neural pathways. Using a visuomotor decision-making task, we show that participants differentially utilized online perceptual decision-making in reaching and interception, and that eye movements necessary for perception influenced motor decision strategies. These results provide evidence that task complexity modulates how pathways processing perception versus action information interact during the visual control of movement.
Bacterial metabolism rescues the inhibition of intestinal drug absorption by food and drug additives
Authors: Zou Ling , Spanogiannopoulos Peter , Chien Huan-Chieh , Pieper Lindsey M. , Cai Wenlong , Khuri Natalia , Pottel Joshua , Vora Bianca , Ni Zhanglin , Tsakalozou Eleftheria , Zhang Wenjun , Shoichet Brian K. , Giacomini Kathleen M. , Turnbaugh Peter J. 
Published: October 2019

AbstractFood and drugs contain diverse small molecule additives (excipients) with unclear impacts on human physiology. Here, we evaluate their potential impact on intestinal absorption, screening 136 unique compounds for inhibition of the key transporter OATP2B1. We identified and validated 24 potent OATP2B1 transport inhibitors, characterized by higher molecular weight and hydrophobicity compared to poor or non-inhibitors. OATP2B1 inhibitors were also enriched for dyes, including 8 azo (R−N=N−R′) dyes. Pharmacokinetic studies in mice confirmed that FD&C Red No. 40, a common azo dye excipient, inhibited drug absorption; however, the human gut microbiome inactivated azo dye excipients, producing metabolites that no longer inhibit OATP2B1 transport. These results support a beneficial role for the microbiome in limiting the unintended effects of food and drug additives in the intestine.One Sentence SummaryFood and drug additives inhibit intestinal drug transporters, although some are inactivated by gut bacterial metabolism.
An improved molecular tool for screening bacterial colonies using GFP expression enhanced by aDictyosteliumsequence
Authors: Kondo Tomo , Yumura Shigehiko 
Published: October 2019

AbstractDuring molecular cloning, screening of bacterial transformants is a time-consuming and labor-intensive process. However, tractable tools that can be applied to various vectors for visual confirmation of desired colonies are limited. Recently, we reported that TED (translational enhancement by aDictyosteliumgene sequence) boosted protein expression even without an expression inducer inEscherichia coli. Here, we demonstrate a generally applicable molecular tool using the expression of green fluorescent protein (GFP) enhanced by TED. By inserting a module related to TED into the cloning site in advance, we effectively screenedE. colicolonies harboring the desired plasmid functions in a prokaryote (Magnetospirillum gryphiswaldense) or eukaryote (Dictyostelium discoideum). Thus, our system represents a user-friendly technique for cloning.
The stepwise endonuclease activity of a thermophilic Argonaute protein
Authors: Xun Guanhua , Liu Qian , Chong Yuesheng , Li Zhonglei , Guo Xiang , Li Yinhua , Fei He , Li Kai , Feng Yan 
Published: October 2019

AbstractThermophilic Argonaute proteins (Agos) can function as endonucleases via specific guide-target base-pairing cleavage for host defense. The ability to cleave target DNA sequences at any arbitrary sites endows them with reprogramed DNA capacity. Here, we identify that an Ago from the hyperthermophilic archaeon Pyrococcus furiosus (PfAgo) shows a stepwise endonuclease activity, which is demonstrated by the double strand DNA cleavage directed by a single guide DNA rather than canonical one pair of guide DNAs. We reveal that the cleavage products with 5’-phosphorylated ends can used as the renewed guide which is capable to induce next round of cleavage to complementary sequences of target DNA. By combining the PfAgo stepwise endonuclease activity followed by target DNA amplification, we establish a rapid and specific platform for the unambiguously multiplex gene detection, termed RADAR (Renewed-gDNA Assisted DNA-cleavage by Argonaute). In the end, RADAR was applied to distinguish of human papillomavirus of serotypes in patient samples in a single reaction, suggesting that our technique would be adopted for diagnosing application.
The methyltransferase DOT1L limits activation and the Th1 program in CD4+T cells during infection and inflammation
Authors: Scheer Sebastian , Runting Jessica , Bramhall Michael , Russ Brendan , Zaini Aidil , Ellemor Jessie , Rodrigues Grace , Ng Judy , Zaph Colby 
Published: October 2019

AbstractCD4+T helper (Th) cell differentiation is controlled by lineage-specific expression of transcription factors and effector proteins, as well as silencing of lineage-promiscuous genes. Lysine methyltransferases (KMTs) comprise a major class of epigenetic enzymes that are emerging as important regulators of Th cell biology. Here, we show that the KMT DOT1L regulates Th cell function and lineage integrity. DOT1L-dependent dimethylation of lysine 79 of histone H3 (H3K79me2) is associated with lineage-specific gene expression. However, DOT1L-deficient Th cells overproduce IFN-γ under lineage-specific and lineage-promiscuous conditions. Consistent with the increased IFN-γ response, mice with a T cell-specific deletion of DOT1L are susceptible to infection with the helminth parasiteTrichuris murisand resistant to the development of allergic lung inflammation. These results identify a central role for DOT1L in Th cell lineage commitment and stability, and suggest that inhibition of DOT1L may provide a novel therapeutic strategy to limit type 2 immune responses.
Differential expression of deltaFosB in reward processing regions between binge eating prone and resistant female rats
Authors: Amissah Richard Quansah , Chometton Sandrine , Calvez Juliane , Guèvremont Genevieve , Timofeeva Elena , Timofeev Igor 
Published: October 2019

AbstractBinge eating disorder (BED) is characterized by bingeing and compulsivity. Even though BED is the most prevalent eating disorder, little is known about its pathophysiology. We aimed to identify brain regions and neuron subtypes implicated in the development of binge-like eating in a female rat model. We separated rats into binge eating prone (BEP) and binge eating resistant (BER) phenotypes based on the amount of sucrose they consumed following foot-shock stress. We quantified deltaFosB (ΔFosB) expression to assess chronic neuronal activation during phenotyping. The number of ΔFosB-expressing neurons was: 1) higher in BEP than BER rats in reward processing areas (medial prefrontal cortex (mPFC), nucleus accumbens (Acb), and ventral tegmental area (VTA)); 2) similar in taste processing areas (insular cortex and parabrachial nucleus); 3) higher in the paraventricular nucleus of BEP than BER rats, but not different in the locus coeruleus, which are stress processing structures. To study subtypes of ΔFosB-expressing neurons in the reward system, we performed in situ hybridization for glutamate decarboxylase 65 and tyrosine hydroxylase mRNA after ΔFosB immunohistochemistry. In the mPFC and Acb, the proportions of gamma-aminobutyric acidergic (GABAergic) and non-GABAergic ΔFosB-expressing neurons were similar in BER and BEP rats. In the VTA, while the proportion of dopaminergic ΔFosB-expressing neurons was similar in both phenotypes, the proportion of GABAergic ΔFosB-expressing neurons was higher in BER than BEP rats. Our results suggest that reward processing brain regions, particularly the VTA, are important for the development of binge-like eating.SignificanceBecause ΔFosB expression is associated with a reduction of activity in neurons, a higher expression of ΔFosB in the mPFC, Acb, and VTA of binge eating prone rats compared to binge eating resistant rats suggests a decrease in neuronal activity in these regions, which is consistent with results observed in neuroimaging studies in binge eating disorder patients. This decrease in activity due to ΔFosB expression may underlie the compulsivity and overconsumption of palatable food observed in both our rat model of binge-like eating and binge eating disorder patients.
The spliceosome inhibitors isoginkgetin and pladienolide B induce ATF3-dependent cell death
Authors: Vanzyl Erin J. , Sayed Hadil , Blackmore Alex B. , Rick Kayleigh R.C. , Fernando Pasan , McKay Bruce C. 
Published: October 2019

AbstractThe spliceosome assembles on pre-mRNA in a stepwise manner through five successive pre-spliceosome complexes. The spliceosome functions to remove introns from pre-mRNAs to generate mature mRNAs that encode functional proteins. Many small molecule inhibitors of the spliceosome have been identified and they are cytotoxic. However, little is known about genetic determinants of cell sensitivity. Activating transcription factor 3 (ATF3) is a transcription factor that can stimulate apoptotic cell death in response to a variety of cellular stresses. Here, we used a genetic approach to determine if ATF3 was important in determining the sensitivity of mouse embryonic fibroblasts (MEFs) to two splicing inhibitors: pladienolide B (PB) and isoginkgetin (IGG), that target different pre-spliceosome complexes. Both compounds led to increased ATF3 expression and apoptosis in control MEFs while ATF3 null cells were significantly protected from the cytotoxic effects of these drugs. Similarly, ATF3 was induced in response to IGG and PB in the two human tumour cell lines tested while knockdown of ATF3 protected cells from both drugs. Taken together, ATF3 appears to contribute to the cytotoxicity elicited by these spliceosome inhibitors in both murine and human cells.
Social and endogenous infant vocalizations
Authors: Long Helen L. , Bowman Dale , Yoo Hyunjoo , Burkhardt-Reed Megan M. , Bene Edina R. , Oller D. Kimbrough 
Published: October 2019

AbstractResearch on infant vocal development has provided notable insights into vocal interaction with caregivers, elucidating growth in foundations for language through parental elicitation and reaction to vocalizations. A role for infant vocalizations produced endogenously, potentially providing raw material for interaction and a basis for growth in the vocal capacity itself, has received less attention. We report that in laboratory recordings of infants and their parents, the bulk of infant speech-like vocalizations, or “protophones”, were directed toward no one and instead appeared to be generated endogenously, mostly in exploration of vocal abilities. The tendency to predominantly produce protophones without directing them to others occurred both during periods when parents were instructed to interact with their infantsandduring periods when parents were occupied with an interviewer, with the infants in the room. The results emphasize the infant as an agent in vocal learning, even when not interacting socially and suggest an enhanced perspective on foundations for vocal language.
Screening of Tau Protein Kinase Inhibitors in a Tauopathy-relevant cell-based model of Tau Hyperphosphorylation and Oligomerization
Authors: Yadikar Hamad , Torres Isabel , Aiello Gabrielle , Kurup Milin , Yang Zhihui , Lin Fan , Kobeissy Firas , Yost Richard , Wang Kevin K. 
Published: October 2019

ABSTRACTTauopathies are a class of neurodegenerative disorders characterized by abnormal deposition of post-translationally modified tau protein in the human brain. Tauopathies are associated with Alzheimer’s disease (AD), chronic traumatic encephalopathy (CTE), and other diseases. Hyperphosphorylation increases tau tendency to aggregate and forms neurofibrillary tangles (NFT), a pathological hallmark of AD. In this study, okadaic acid (OA, 100 nM), a protein phosphatase 1/2A inhibitor, was treated for 24h in mouse neuroblastoma (N2a) and differentiated rat primary neuronal cortical cell cultures (CTX) to induce tau-hyperphosphorylation and oligomerization as a cell-based tauopathy model. Following the treatments, the effectiveness of different kinase inhibitors was assessed using the tauopathy-relevant tau antibodies through tau-immunoblotting, including the sites: pSer202/pThr205 (AT8), pThr181 (AT270), pSer202 (CP13), pSer396/pSer404 (PHF-1), and pThr231 (RZ3). OA-treated samples induced tau phosphorylation and oligomerization at all tested epitopes, forming a monomeric band (46-67 kDa) and oligomeric bands (170 kDa and 240 kDa). We found that TBB (a casein kinase II inhibitor), AR and LiCl (GSK-3 inhibitors), cyclosporin A (calcineurin inhibitor), and Saracatinib (Fyn kinase inhibitor) caused robust inhibition of OA-induced monomeric and oligomeric p-tau in both N2a and CTX culture. Additionally, a cyclin-dependent kinase 5 inhibitor (Roscovitine) and a calcium chelator (EGTA) showed conflicting results between the two neuronal cultures.This study provides a comprehensive view of potential drug candidates (TBB, CsA, AR, and Saracatinib), and their efficacy against tau hyperphosphorylation and oligomerization processes. These findings warrant further experimentation, possibly including animal models of tauopathies, which may provide a putative Neurotherapy for AD, CTE, and other forms of tauopathy-induced neurodegenerative diseases.
Divergent excitation two photon microscopy for 3D random access mesoscale imaging at single cell resolution
Authors: Janiak FK , Bartel P , Bale MR , Yoshimatsu T , Komulainen E , Zhou M , Staras K , Prieto-Godino LL , Euler T , Maravall M , Baden T 
Published: October 2019

ABSTACTIn neuroscience, diffraction limited two-photon (2P) microscopy is a cornerstone technique that permits minimally invasive optical monitoring of neuronal activity. However, most conventional 2P microscopes impose significant constraints on the size of the imaging field-of-view and the specific shape of the effective excitation volume, thus limiting the scope of biological questions that can be addressed and the information obtainable. Here, employing ‘divergent beam optics’ (DBO), we present an ultra-low-cost, easily implemented and flexible solution to address these limitations, offering a several-fold expanded three-dimensional field of view that also maintains single-cell resolution. We show that this implementation increases both the space-bandwidth product and effective excitation power, and allows for straight-forward tailoring of the point-spread-function. Moreover, rapid laser-focus control via an electrically tunable lens now allows near-simultaneous imaging of remote regions separated in three dimensions and permits the bending of imaging planes to follow natural curvatures in biological structures. Crucially, our core design is readily implemented (and reversed) within a matter of hours, and fully compatible with a wide range of existing 2P customizations, making it highly suitable as a base platform for further development. We demonstrate the application of our system for imaging neuronal activity in a variety of examples in mice, zebrafish and fruit flies.