bluuebunny/crossref_metadata_2025_split huggingface dataset:
Disruption of cortical dopaminergic modulation impairs preparatory activity and delays licking initiation
Authors: Chen Ke , Vincis Roberto , Fontanini Alfredo 
Published: June 2018

ABSTRACTDysfunction of motor cortices is thought to contribute to motor disorders such as Parkinson’s disease (PD). However, little is known on the link between cortical dopaminergic loss, abnormalities in motor cortex neural activity and motor deficits. We address the role of dopamine in modulating motor cortical activity by focusing on the anterior lateral motor cortex (ALM) of mice performing a cued-licking task. We first demonstrate licking deficits and concurrent alterations of spiking activity in ALM of mice with unilateral depletion of dopaminergic neurons (i.e., mice injected with 6-OHDA into the medial forebrain bundle). Hemi-lesioned mice displayed delayed licking initiation, shorter duration of licking bouts, and lateral deviation of tongue protrusions. In parallel with these motor deficits, we observed a reduction in the prevalence of cue responsive neurons and altered preparatory activity. Acute and local blockade of D1 receptors in ALM recapitulated some of the key behavioral and neural deficits observed in hemi-lesioned mice. Altogether, our data show a direct relationship between cortical D1 receptor modulation, cue-evoked and preparatory activity in ALM, and licking initiation.SIGNIFICANCE STATEMENTThe link between dopaminergic signaling, motor cortical activity and motor deficits is not fully understood. This manuscript describes alterations in neural activity of the anterior lateral motor cortex (ALM) that correlate with licking deficits in mice with unilateral dopamine depletion or with intra-ALM infusion of dopamine antagonist. The findings emphasize the importance of cortical dopaminergic modulation in motor initiation. These results will appeal not only to researchers interested in cortical control of licking, but also to a broader audience interested in motor control and dopaminergic modulation in physiological and pathological conditions. Specifically, our data suggest that dopamine deficiency in motor cortex could play a role in the pathogenesis of the motor symptoms of Parkinson’s disease.
Smaller Hippocampal CA-1 Subfield Volume in Posttraumatic Stress Disorder
Authors: Chen Lyon W. , Sun Delin , Davis Sarah L. , Haswell Courtney C. , Dennis Emily L. , Swanson Chelsea A. , Whelan Christopher D. , Gutman Boris , Jahanshad Neda , Iglesias Juan Eugenio , Thompson Paul ,   Mid-Atlantic MIRECC Workgroup, Wagner H. Ryan , Saemann Philipp , LaBar Kevin S. , Morey Rajendra A. 
Published: June 2018

AbstractBackgroundSmaller hippocampal volume in patients with PTSD represents the most consistently reported structural alteration in the brain. Subfields of the hippocampus play distinct roles in encoding and processing of memories, which are disrupted in PTSD. We examined PTSD-associated alterations in 12 hippocampal subfields in relation to global hippocampal shape, and clinical features.MethodsCase-control cross-sectional study of US military veterans (n=282) from the Iraq and Afghanistan era were grouped into PTSD (n=142) and trauma-exposed controls (n=140). Participants underwent clinical evaluation for PTSD and associated clinical parameters followed by MRI at 3-Tesla. Segmentation with Free Surfer v6.0 produced hippocampal subfield volumes for the left and right CA1, CA3, CA4, DG, fimbria, fissure, hippocampus-amygdala transition area, molecular layer, parasubiculum, presubiculum, subiculum, and tail, as well as hippocampal meshes. Covariates included age, gender, trauma exposure, alcohol use, depressive symptoms, antidepressant medication use, total hippocampal volume, and MRI scanner model.ResultsSignificantly lower subfield volumes were associated with PTSD in left CA1 (p=.01; d=.21; uncorrected), CA3 (p=.04; d=.08; uncorrected), and right CA3 (p=.02; d=.07; uncorrected) only if ipsilateral whole hippocampal volume was included as a covariate. A trend level association of L-CA1 with PTSD [F4,221=3.32, p = 0.07] is present and the other subfield findings are non-significant if ipsilateral whole hippocampal volume is not included as a covariate. PTSD associated differences in global hippocampal shape were non-significant.ConclusionsThe present finding of smaller hippocampal CA1 in PTSD is consistent with model systems in rodents that exhibit increased anxiety-like behavior from repeated exposure to acute stress. Behavioral correlations with hippocampal subfield volume differences in PTSD will elucidate their relevance to PTSD, particularly behaviors of associative fear learning, extinction training, and formation of false memories.
Chronic intermittent ethanol exposure selectively increases synaptic excitability in the ventral domain of the rat hippocampus
Authors: Ewin Sarah E. , Morgan James W. , Niere Farr , McMullen Nate P. , Barth Samuel H. , Almonte Antoine G. , Raab-Graham Kimberly F. , Weiner Jeffrey L. 
Published: June 2018

AbstractMany studies have implicated hippocampal dysregulation in the pathophysiology of alcohol use disorder (AUD). However, over the past twenty years, a growing body of evidence has revealed distinct functional roles of the dorsal (dHC) and ventral (vHC) hippocampal subregions, with the dHC being primarily involved in spatial learning and memory and the vHC regulating anxiety-and depressive-like behaviors. Notably, to our knowledge, no rodent studies have examined the effects of chronic ethanol exposure on synaptic transmission along the dorsal/ventral axis. To that end, we examined the effects of the chronic intermittent ethanol vapor exposure (CIE) model of AUD on dHC and vHC synaptic excitability. Adult male Long-Evans rats were exposed to CIE or air for 10 days (12 hrs/day; targeting blood ethanol levels of 175-225 mg%) and recordings were made 24 hours into withdrawal. As expected, this protocol increased anxiety-like behaviors on the elevated plus-maze. Extracellular recordings revealed marked CIE-associated increases in synaptic excitation in the CA1 region that were exclusively restricted to the ventral domain of the hippocampus. Western blot analysis of synaptoneurosomal fractions revealed that the expression of two proteins that regulate synaptic strength, GluA2 and SK2, was dysregulated in the vHC, but not the dHC, following CIE. Together, these findings suggest that the ventral CA1 region may be particularly sensitive to the maladaptive effects of chronic ethanol exposure and provide new insight into some of the neural substrates that may contribute to the negative affective state that develops during withdrawal.HighlightsChronic intermittent ethanol exposure produces robust increases in anxiety-like behavior in male Long Evans rats.Chronic intermittent ethanol exposure increases synaptic excitability in the ventral, but not the dorsal, domain of the hippocampus.These changes in excitability are associated with alterations in synaptoneurosomal expression of small conductance calcium-activated potassium channels and the GluA2 AMPA receptor subunit that are also restricted to the ventral hippocampus.
MHC Genetic Variation Influences both Olfactory Signals and Scent Discrimination in Ring-Tailed Lemurs
Authors: Grogan Kathleen E. , Harris Rachel L. , Boulet Marylène , Drea Christine M. 
Published: June 2018

ABSTRACTDiversity at the Major Histocompatibility Complex (MHC) is critical to health and fitness, such that MHC genotype may predict an individual’s quality or compatibility as a competitor, ally, or mate. Moreover, because MHC products can influence the components of bodily secretions, an individual’s body odor may signal its MHC and influence partner identification or mate choice. To investigate MHC-based signaling and recipient sensitivity, we test for odor-gene covariance and behavioral discrimination of MHC diversity and pairwise dissimilarity, under the good genes and good fit paradigms, in a strepsirrhine primate, the ring-tailed lemur (Lemur catta). First, we coupled genotyping with gas chromatography-mass spectrometry to investigate if diversity of the MHC-DRB gene is signaled by the chemical diversity of lemur genital scent gland secretions. We also assessed if the chemical similarity between individuals correlated with their MHC similarity. Next, we assessed if lemurs discriminated this chemically encoded, genetic information in opposite-sex conspecifics. We found that both sexes signaled overall MHC diversity and pairwise MHC similarity via genital secretions, but in a sex- and season-dependent manner. Additionally, both sexes discriminated absolute and relative MHC-DRB diversity in the genital odors of opposite-sex conspecifics, supporting previous findings that lemur genital odors function as advertisement of genetic quality. In this species, genital odors provide honest information about an individual’s absolute and relative MHC quality. Complementing evidence in humans and Old World monkeys, our results suggest that reliance on scent signals to communicate MHC quality may be important across the primate lineage.
TuxNet: A simple interface to process RNA sequencing data and infer gene regulatory networks
Authors: Luis Balaguer Maria Angels de , Spurney Ryan J. , Clark Natalie M. , Fisher Adam P. , Sozzani Rosangela 
Published: June 2018

ABSTRACTPredicting gene regulatory networks (GRNs) from gene expression profiles has become a common approach for identifying important biological regulators. Despite the increase in the use of inference methods, existing computational approaches do not integrate RNA-sequencing data analysis, are often not automated, and are restricted to users with bioinformatics and programming backgrounds. To address these limitations, we have developed TuxNet, an integrated user-friendly platform, which, with just a few selections, allows to process raw RNA-sequencing data (using the Tuxedo pipeline) and infer GRNs from these processed data. TuxNet is implemented as a graphical user interface and, using expression data from any organism with an existing reference genome, can mine the regulations among genes either by applying a dynamic Bayesian network inference algorithm, GENIST, or a regression tree-based pipeline that uses spatiotemporal data, RTP-STAR. To illustrate the use of TuxNet while getting insight into the regulatory cascade downstream of the Arabidopsis root stem cell regulator PERIANTHIA (PAN), we obtained time course gene expression data of a PAN inducible line and inferred a GRN using GENIST. Using RTP-STAR, we then inferred the network of a PAN secondary downstream gene, ATHB13, for which we obtained wildtype and mutant expression profiles. Our case studies feature the versatility of TuxNet to infer networks using different types of gene expression data (i.e time course and steady-state data) as well as how inference networks are used to identify important regulators.SUMMARYTuxNet offers a simple interface for non-computational biologists to infer GRNs from raw RNA-seq data.
β-cyclocitral is a conserved root growth regulator
Authors: Dickinson Alexandra J. , Lehner Kevin , Mi Jianing , Jia Kun-Peng , Mijar Medhavinee , Dinneny José , Al-Babili Salim , Benfey Philip N. 
Published: June 2018

AbstractNatural compounds capable of increasing root depth and branching are desirable tools for enhancing stress tolerance in crops. We devised a sensitized screen to identify natural metabolites capable of regulating root traits in Arabidopsis. β-cyclocitral, an endogenous root compound, was found to promote cell divisions in root meristems and stimulate lateral root branching. β-cyclocitral rescued meristematic cell divisions inccd1ccd4biosynthesis mutants and β-cyclocitral-driven root growth was found to be independent of auxin, brassinosteroid, and ROS signaling pathways. β-cyclocitral had a conserved effect on root growth in tomato and rice and generated significantly more compact crown root systems in rice. Moreover, β-cyclocitral treatment enhanced plant vigor in rice plants exposed to salt-contaminated soil. These results indicate that β-cyclocitral is a broadly effective root growth promoter in both monocots and eudicots and could be a valuable tool to enhance crop vigor under environmental stress.One Sentence Summaryβ-cyclocitral is a metabolite of β-carotene that was identified using a sensitized chemical screen and acts broadly across plants to enhance root growth and branching.
An examination of the evolve-and-resequence method usingDrosophila simulans
Authors: Kelly John K. , Hughes Kimberly A. 
Published: June 2018

AbstractWe develop a set of analytical and simulation tools for Evolve-and-Resequence (E&R) experiments and apply them to a new study of rapid evolution inDrosophila simulans. Likelihood based test statistics applied to pooled population sequencing data suggest parallel evolution of 138 polymorphisms (SNPs) across the genome. This number is reduced by orders of magnitude from previous studies (thousands or tens of thousands), owing to differences in both experimental design and statistical analysis. Whole genome simulations calibrated from several Drosophila genetic datasets support the contention that the observed genome-wide response could be generated by as few as 30 loci under strong directional selection, with a corresponding hitch-hiking effect. Finally, the SNPs that showed strong parallel evolution in the novel laboratory environment exhibit an (initial) allele frequency spectrum indicative of balancing in nature. These loci also exhibit elevated differentiation among natural populations ofD. simulans.
Life history trade-offs in ectotherms impart a pseudo-hormetic response, not hormesis
Authors: McCallum Malcolm L. , Mary Michelle , Trauth Stanley E. 
Published: June 2018

AbstractAll organisms are faced with survival and fitness challenges. However, differences in how ectotherms and endotherms deal with these challenges causes confusion when theoretical explanations are proposed. Herein, an immunochallenged, immature ectothermic vertebrate increased growth in the face of immunochallenge, reminiscent of up-regulated physiological efficiency termed hormesis. The immunochallenged subjects increased food intake relative to control animals, a largely ignored possibility in previous studies. This likely led to an energy surplus that fueled additional growth. Although there was increased resource demand from the immune response that exceeded internal stores, the acceptably sized food items contained more resources than immunologically-driven demand required. We theorize that because ectotherms lack significant internally-stored resources compared to endotherms, they must feed to fuel increased physiological demand. This can lead to excess resource intake because the minimum acceptably sized prey contains more available resources than upregulation required. This creates a pseudo-hormetic hormetic response, fueled by excess food intake rather than significant improved physiological efficiency. Further, we speculate that lifespan and/or maturity may interact with resource management ectotherms, though our data are inconclusive on this matter. Ultimately, our data suggest additional growth when ectotherms face stressors is a pseudo-hormetic response stemming from increased food intake instead of upregulated physiological efficiency.
Competition and Synergy BetweenProchlorococcusandSynechococcusUnder Ocean Acidification Conditions
Authors: Knight Margaret A. , Morris J. Jeffrey 
Published: June 2018

ABSTRACTAnthropogenic CO2emissions are projected to lower the pH of the open ocean by 0.2 to 0.3 units over the next century. Laboratory experiments show that different phytoplankton taxa exhibit a wide variety of responses, with some strains having higher fitness under projected future conditions, and others being negatively impacted. Previous studies have suggested thatProchlorococcusandSynechococcus, the numerically dominant picophytoplankton in the oceans, have very different responses to elevated CO2that may result in a dramatic shift in their relative abundances in future oceans. Here we show that these two genera experience faster exponential growth rates under future CO2conditions, similar to most other cyanobacteria that have been studied. However,Prochlorococcusstrains have significantly lower realized growth rates due to more extreme lag periods after exposure to fresh culture media. Surprisingly, however,Synechococcuswas unable to outcompeteProchlorococcusin co-culture at elevated CO2. Under these conditions,Prochlorococcus’ poor response to elevated CO2disappeared, and it showed negative frequency dependence in its relative fitness compared toSynechococcus, with a significant fitness advantage when it was initially rare. Moreover, bothSynechococcusandProchlorococcushad faster growth rates in co-culture with each other than either had in unialgal culture. We speculate that this negative frequency dependence is an outgrowth of reductive Black Queen evolution operating on both taxa that has resulted in a passively mutualistic relationship analogous to that connectingProchlorococcuswith the “helper” heterotrophic microbes in its environment.
Nitrogen utilization and transformation ofStenotrophomonas maltophiliaW-6 with nitrogen-fixing ability
Authors: Wang Shutong , Xu Yi , Li Zhenlun 
Published: June 2018

AbstractStrain W-6 was isolated from the purple soil and successfully identifed asStenotrophomonas maltophiliaand used for the investigation on nitrogen utilization. Strain W-6 was monitored with the ability of biological nitrogen fixation when N2was used for the sole nitrogen source, and yet nitrogenase activity would be inhibited in the presence of extra nitrogen. Moreover, Strain W-6 could utilize NO3−, NO2−and NH4+for cell growth through assimilation, but unable to convert them to atmospheric nitrogen. Meantime, accumulation of nitrite was observed during the nitrate removal process, and the optimal conditions for nitrate removal were temperature of 20°C, shaking speed of 150 rpm, sodium succinate as the carbon source and C/N of 12. The experimental results indicate thatStenotrophomonas maltophiliautilize W-6 could utilize not only N2but also other nitrogen sources directly as its N substance. Therefore, heterotrophicAzotobactermay possess a great significance to nitrogen cycle except in biological nitrogen fixation.ImportanceAzotobacterspp. are found in soils worldwide, with features not simply for the nitrogen fixation, but for the energy metabolism relevant to agriculture. However, the role ofAzotobacterpotential in the function of nitrogen cycle except in biological nitrogen fixation is largely unknown. As such, whether bacteria utilize either inorganic nitrogen or organic nitrogen has remained obscure. The present studies indicate thatStenotrophomonas maltophiliaW-6 could highly efficient utilize nitrate, nitrite and ammonium etc. N substance and detect NH4+as final product. The transport velocities of nitrate-N to nitrite-N was quickly without gaseous nitrogen was produced. We probed the relationship between biological nitrogen fixation and N cycle via N conversion processes byS. maltophiliaW-6 with nitrogen-fixing ability
Impact of efavirenz, ritonavir-boosted lopinavir and nevirapine based antiretroviral regimens on the pharmacokinetics of lumefantrine and safety of artemether-lumefantrine in falciparum-negative HIV-infected Malawian adults stabilized on antiretroviral therapy
Authors: Banda Clifford George , Dzinjalamala Fraction , Mukaka Mavuto , Mallewa Jane , Maiden Victor , Terlouw Dianne J , Lalloo David G. , Khoo Saye H. , Mwapasa Victor 
Published: June 2018

ABSTRACTThere is conflicting evidence of the impact of commonly used antiretroviral therapies (ARTs) on the pharmacokinetics of lumefantrine and safety profile of artemether-lumefantrine. We compared the area under the concentration-time curve (AUC0-14 days) of lumefantrine and safety profile of artemether-lumefantrine in malaria-negative human immunodeficiency virus (HIV) infected adults in two steps. In step 1, a half-dose adult course of artemether-lumefantrine was administered as a safety check in four groups (n = 6/group): (i) antiretroviral-naïve, (ii) on nevirapine-based ART, (iii) on efavirenz-based ART and (iv) on ritonavir-boosted lopinavir-based ART. In step 2, a standard-dose adult course of artemether-lumefantrine was administered to a different cohort in three groups (n = 10–15/group): (i) antiretroviral-naïve, (ii) on efavirenz-based ART and (iii) on ritonavir-boosted lopinavir-based ART. In step 1, lumefantrine’s AUC0-14 days was 53% [95% CI: 0.27-0.82] lower in the efavirenz-based ART group than the ART-naïve group and was 2.4 [95% CI: 1.58-3.62] and 2.9 [95% CI: 1.75-4.72] times higher in the nevirapine and ritonavir-boosted lopinavir groups, respectively. In step 2, lumefantrine’s AUC0-14 days was 1.9 [95% CI: 1.26-3.00] times higher in the ritonavir-boosted lopinavir group and not significantly different between the efavirenz-and ART-naïve groups (0.99 [95% CI: 0.63-1.57]). Frequent cases of haematological abnormalities (thrombocytopenia and neutropenia) were observed in the nevirapine group in step 1, leading to a recommendation from the data and safety monitoring board not to include a nevirapine group in step 2. Artemether-lumefantrine was well tolerated in the other groups. The therapeutic implications of these findings need to be evaluated among HIV-malaria co-infected adults.
Genome plasticity in Papillomaviruses andde novoemergence ofE5oncogenes
Authors: Willemsen Anouk , Félez-Sánchez Marta , Bravo Ignacio G. 
Published: June 2018

AbstractThe clinical presentations of papillomavirus (PV) infections come in many different flavors. While most PVs are part of a healthy skin microbiota and are not associated to physical lesions, other PVs cause benign lesions, and only a handful of PVs are associated to malignant transformations linked to the specific activities of theE5,E6andE7oncogenes. The functions and origin ofE5remain to be elucidated. TheseE5ORFs are present in the genomes of a few polyphyletic PV lineages, located between the early and the late viral gene cassettes. We have computationally assessed whether theseE5ORFs have a common origin and whether they display the properties of a genuine gene. Our results suggest that during the evolution ofPapillomaviridae, at least four events lead to the presence of a long non-coding DNA stretch between theE2and theL2genes. In three of these events, the novel regions evolved coding capacity, becoming the extantE5ORFs. We then focused on the evolution of theE5genes inAlphaPVsinfecting humans. The sharp match between the type of E5 protein encoded inAlphaPVsand the infection phenotype (cutaneous warts, genital warts or anogenital cancers) supports the role of E5 in the differential oncogenic potential of these PVs. In our analyses, the best-supported scenario is that the five types of extant E5 proteins within theAlphaPVgenomes may not have a common ancestor. However, the chemical similarities between E5s regarding amino acid composition prevent us from confidently rejecting the model of a common origin. Our evolutionary interpretation is that an originally non-coding region entered the genome of the ancestralAlphaPVs. This genetic novelty allowed to explore novel transcription potential, triggering an adaptive radiation that yielded three main viral lineages encoding for different E5 proteins, and that display distinct infection phenotypes. Overall, our results provide an evolutionary scenario for thede novoemergence of viral genes and illustrate the impact of such genotypic novelty in the phenotypic diversity of the viral infections.