bluuebunny/crossref_metadata_2025_split huggingface dataset:
P2X antagonists inhibit HIV-1 productive infection and inflammatory cytokines IL-10 and IL-1β in a human tonsil explant model
Authors: Soare Alexandra Y. , Durham Natasha D. , Gopal Ramya , Tweel Benjamin , Hoffman Kevin W. , Brown Julia A. , O’Brien Megan , Bhardwaj Nina , Lim Jean K. , Chen Benjamin K. , Swartz Talia H. 
Published: July 2018

AbstractHIV-1 causes a persistent infection of the immune system that is associated with chronic comorbidities. The mechanisms that underlie this inflammation are poorly understood. Emerging literature has implicated pro-inflammatory purinergic receptors and downstream signaling mediators in HIV-1 infection. This study probed whether inhibitors of purinergic receptors would reduce HIV-1 infection and HIV-1 stimulated inflammation. A human ex vivo human tonsil histo-culture infection model was developed to support HIV-1 productive infection and stimulated inflammatory cytokine interleukin-1 beta (IL-1β) and immunosuppressive cytokine, interleukin-10 (IL-10). This study tests whether inhibitors of purinergic receptors would reduce HIV-1 infection and HIV-1 stimulated inflammation. The purinergic P2X1 receptor antagonist, NF449, the purinergic P2X7 receptor antagonists, A438079, and azidothymidine (AZT) were tested in HIV-1 infected human tonsil explants to compare inhibition of HIV-1 infection and HIV-stimulated inflammatory cytokine production. All drugs limited HIV-1 productive infection but P2X-selective antagonists (NF449, and A438079) significantly lowered HIV-stimulated IL-10 and IL-1β. We further observed that P2X1- and P2X7-selective antagonists can act differentially as inhibitors of both HIV-1 infection and HIV-1-stimulated inflammation. Our findings highlight the differential effects of HIV-1 on inflammation in peripheral blood as compared to lymphoid tissue. For the first time, we demonstrate that P2X-selective antagonists act differentially as inhibitors of both HIV-1 infection and HIV-1-stimulated inflammation. Drugs that block these pathways can have independent inhibitory activities against HIV-1 infection and HIV-induced inflammation.ImportancePatients who are chronically infected with HIV-1 experience sequelae related to chronic inflammation. The mechanisms of this inflammation have not been elucidated. Here we describe a class of drugs that target the P2X pro-inflammatory signaling receptors in a human tonsil explant model. This model highlights differences in HIV-1 stimulation of lymphoid tissue inflammation and peripheral blood. These drugs serve to both block HIV-1 infection and production of IL-10 and IL-1β in lymphoid tissue suggesting a novel approach to HIV-1 therapeutics in which both HIV-1 replication and inflammatory signaling are simultaneously targeted.
Bloodstream Infection with Extended-spectrum Beta-lactamase–producingEscherichia coli: the role of virulence genes
Authors: Hung Wan-Ting , Cheng Ming-Fang , Tseng Fan-Chen , Chen Yao-Shen , Lee Susan Shin-Jung , Chang Tsung-Hsien , Lin Hsi-Hsun , Hung Chih-Hsin , Wang Jiun-Ling 
Published: July 2018

AbstractBackgroundVarious bacterial putative virulence factors are involved in the pathogenesis of bacterial infection. However, the effect of comorbidities or infection syndrome in the association of virulence factors and mortality remains inconclusive.MethodThis study addressed whether specific sequence type (ST) and virulence factors of extended-spectrum beta-lactamase–producingEscherichia coli(ESBL-EC) are associated with different outcomes in patients with bloodstream infection.121 adults from southern Taiwan with ESBL-producingE. colibloodstream infections were enrolled during a 6-year period. Demographic data, including infection syndromes, underlying disease and outcomes, were collected. The virulence factors in isolates were analyzed by PCR and multilocus sequence typing.ResultPositivity for the virulence genes iha,hlyD,sat,iut,fyu,malX,ompT,uspandtraTwas associated with ST131 positivity (P<0.05). Some ESBL-EC virulence genes associated with urinary tract infection (UTI) were revealed. Positivity for ST405 and the virulence genesiroNandisswas significantly associated with increased 30-day mortality (death within 30 days) on univariate analysis (P<0.05). Independent risk factors of 30-day mortality in bacteremic patients with UTI included underlying chronic liver disease and malignancy. ST131 was borderline associated with 30-day mortality. Independent risk factors associated with 30-day mortality among bacteremic patients without UTI included comorbidities andiroNpositivity.ConclusionIn bacteremic patients with UTI, and the ST131 clone was borderline associated with mortality. Positivity for the virulence geneiroNmay be linked to mortality in bacteremic patients without UTI.
How Mg2+stimulates DNA repair in prokaryotic (6-4) photolyases
Authors: Ma Hongju , Holub Daniel , Gillet Natacha , Kaeser Gero , Thoulass Katharina , Elstner Marcus , Krauß Norbert , Lamparter Tilman 
Published: July 2018

AbstractProkaryotic (6-4) photolyases branch at the base of the evolution of cryptochromes and photolyases. In theAgrobacterium(6-4) photolyase PhrB, the repair of DNA with UV-induced (6-4) pyrimidin dimers is stimulated by Mg2+. We show that Mg2+is required for efficient lesion binding and for charge stabilization after electron transfer from the FADH-chromophore to the DNA lesion. Two highly conserved Asp residues close to the DNA binding site are essential for the Mg2+effect. Simulations showed that two Mg2+bind to the region around these residues. DNA repair by eukaryotic (6-4) photolyases is not increased by Mg2+. Here, the structurally overlapping region contains no Asp but positively charged Lys or Arg. During evolution, charge stabilization and DNA binding by Mg2+was therefore replaced by a positive amino acid. We argue that this transition has evolved in a freshwater environment. Prokaryotic (6-4) photolyases usually contain an FeS cluster. DNA repair of a cyanobacterial member of this group which is missing the FeS cluster was also found to be stimulated by Mg2+.
Multipurpose virtual reality environment for biomedical and health applications
Authors: Torner Jordi , Skouras Stavros , Molinuevo José L. , Gispert Juan D. , Alpiste Francisco 
Published: July 2018

AbstractVirtual reality is a trending, widely accessible, contemporary technology of increasing utility to biomedical and health applications. However, most implementations of VR environments are tailored to specific applications. We describe the complete development of a novel, open-source virtual reality environment that is suitable for multipurpose biomedical and healthcare applications. The developed environment simulates an immersive (first-person perspective) run in the countryside, in a virtual landscape with various salient features. The utility of the developed VR environment has been validated via two test usage cases: an application in the context of motor rehabilitation following injury of the lower limbs and an application in the context of real-time functional magnetic resonance imaging neurofeedback, to regulate brain function in specific regions of interest. The resulting test applications suggest that the implemented approach is robust, versatile and efficient. Both applications are publicly available via a GitHub repository, in support of the Open Science initiative. We anticipate our contribution to catalyze further progress and replicability with regards to the usage of virtual reality in biomedical and health applications.Index Terms— Motor rehabilitation, neurofeedback, virtual reality.
Selective axonal translation of prenylated Cdc42 mRNA isoform supports axon growth
Authors: Lee Seung Joon , Kar Amar N. , Zdradzinski Matthew D. , Patel Priyanka , Sahoo Pabitra K. , Kawaguchi Riki , Aguilar Byron J. , Lantz Kelsey D. , McCain Caylee R. , Coppola Giovanni , Lu Qun , Twiss Jeffery L. 
Published: July 2018

ABSTRACTThe small Rho-family GTPase Cdc42 has long been known to have a role in cell motility and axon growth. The eukaryotic CDC42 gene is alternatively spliced to generate mRNAs with two different 3’UTRs that encode proteins with distinct C-termini. The C-termini of these Cdc42 proteins include CAAX and CCAX motifs for post-translational prenylation and palmitoylation, respectively. Palmitoyl-Cdc42 protein was previously shown to contribute to dendrite maturation, while the prenyl-Cdc42 protein contributes to axon specification and its mRNA was detected in neurites. Here, we show that the mRNA encoding prenyl-Cdc42 isoform preferentially localizes into PNS axons and this localization selectively increases in vivo during PNS axon regeneration. Isoform specific siRNA knockdowns, rescue experiments with siRNA-resistant Cdc42 isoforms, and pharmacologically targeting Cdc42 activity indicate that prenyl-Cdc42 promotes axon growth while the palmitoyl-Cdc42 has little growth promoting activity. The growth promotion by prenyl-Cdc42 requires axonal mRNA localization with localized translation and an intact C-terminal CaaX motif for localized prenylation of the encoded protein. Together, these data show that alternative splicing of the CDC42 gene product generates an axon growth promoting locally synthesized prenyl-Cdc42 protein.SUMMARY STATEMENTAxon regeneration drives selective localization of alternatively spliced CDC42 isoform to PNS axons.
Reference Repulsion Is Not a Perceptual Illusion
Authors: Fritsche Matthias , de Langea Floris P. 
Published: July 2018

AbstractPerceptual decisions are often influenced by contextual factors. For instance, when engaged in a visual discrimination task against a reference boundary, subjective reports about the judged stimulus feature are biased away from the boundary – a phenomenon termed reference repulsion. Until recently, this phenomenon has been thought to reflect a perceptual illusion regarding the appearance of the stimulus, but new evidence suggests that it may rather reflect a post-perceptual decision bias. To shed light on this issue, we examined whether and how orientation judgments affect perceptual appearance. In a first experiment, we confirmed that after judging a grating stimulus against a discrimination boundary, the subsequent reproduction response was indeed repelled from the boundary. To investigate the perceptual nature of this bias, in a second experiment we measured the perceived orientation of the grating stimulus more directly, in comparison to a reference stimulus visible at the same time. Although we did observe a small repulsive bias away from the boundary, this bias was explained by random trial-by-trial fluctuations in sensory representations together with classical stimulus adaptation effects and did not reflect a systematic bias due to the discrimination judgment. Overall, the current study indicates that discrimination judgments do not elicit a perceptual illusion and points towards a post-perceptual locus of reference repulsion.
ROCK1/Drp1-mediated aberrant mitochondrial fission is crucial for dopaminergic nerve cell apoptosis
Authors: Zhang Qian , Hu Changpeng , Huang Jingbin , Liu Wuyi , Lai Wenjing , Leng Faning , Tang Qin , Liu Yali , Wang Qing , Zhou Min , Sheng Fangfang , Li Guobing , Zhang Rong 
Published: July 2018

AbstractDopamine deficiency caused by apoptosis of the dopaminergic nerve cells in the midbrain substantia nigra is the main pathological basis of Parkinson's disease (PD). Recent research has shown that dynamin-related protein 1 (Drp1)-mediated aberrant mitochondrial fission plays an important role in dopaminergic nerve cell apoptosis. However, the upstream regulatory mechanism remains unclear. Our study shows that knockdown of Drp1 blocked aberrant mitochondrial fission and dopaminergic nerve cell apoptosis. Importantly, we found that ROCK1 was activated in an MPP+-induced PD cell model and that ROCK1 knockdown and the specific ROCK1 activation inhibitor Y-27632 blocked Drp1-mediated aberrant mitochondrial fission and apoptosis of dopaminergic nerve cell through suppression of Drp1 dephosphorylation/activation. Ourin vivostudy confirmed that Y-27632 significantly improved symptoms of a PD mouse model through inhibition of Drp1-mediated aberrant mitochondrial fission and apoptosis of dopaminergic nerve cell. Collectively, Our study suggests an important molecular mechanism of PD pathogenesis involving ROCK1-regulated dopaminergic nerve cell apoptosis via activation of Drp1-induced aberrant mitochondrial fission.
Neural structure mapping in human probabilistic reward learning
Authors: Luyckx F. , Nili H. , Spitzer B. , Summerfield C. 
Published: July 2018

AbstractHumans can learn abstract concepts that describe invariances over relational patterns in data. One such concept, known as magnitude, allows stimuli to be compactly represented by a single dimension (i.e. on a mental line), for example according to their cardinality, size or value. Here, we measured representations of magnitude in humans by recording neural signals whilst they viewed symbolic numbers. During a subsequent reward-guided learning task, the neural patterns elicited by novel complex visual images reflected their pay-out probability in a way that suggested they were encoded onto the same mental number line. Our findings suggest that in humans, learning about values is accompanied by structural alignment of value representations with neural codes for the concept of magnitude.
Shared Song Detector Neurons in Drosophila Male and Female Brains Drive Sex-Specific Behaviors
Authors: Deutsch David , Clemens Jan , Thiberge Stephan Y. , Guan Georgia , Murthy Mala 
Published: July 2018

AbstractMales and females often produce distinct responses to the same sensory stimuli. How such differences arise – at the level of sensory processing or in the circuits that generate behavior – remains largely unresolved across sensory modalities. We address this issue in the acoustic communication system of Drosophila. During courtship, males generate time-varying songs, and each sex responds with specific behaviors. We characterize male and female behavioral tuning for all aspects of song, and show that feature tuning is similar between sexes, suggesting sex-shared song detectors drive divergent behaviors. We then identify higher-order neurons in the Drosophila brain, called pC2, that are tuned for multiple temporal aspects of one mode of the male’s song, and drive sex-specific behaviors. We thus uncover neurons that are specifically tuned to an acoustic communication signal and that reside at the sensory-motor interface, flexibly linking auditory perception with sex-specific behavioral responses.
The autism-associated gene Scn2a plays an essential role in synaptic stability and learning
Authors: Spratt Perry WE , Ben-Shalom Roy , Keeshen Caroline M , Burke Kenneth J , Clarkson Rebecca L , Sanders Stephan J , Bender Kevin J 
Published: July 2018

SummaryAutism spectrum disorder (ASD) is strongly associated with de novo gene mutations. One of the most commonly affected genes is SCN2A. ASD-associated SCN2A mutations impair the encoded protein NaV1.2, a sodium channel important for action potential initiation and propagation in developing excitatory cortical neurons. The link between an axonal sodium channel and ASD, a disorder typically attributed to synaptic or transcriptional dysfunction, is unclear. Here, we show NaV1.2 is unexpectedly critical for dendritic excitability and synaptic function in mature pyramidal neurons, in addition to regulating early developmental axonal excitability. NaV1.2 loss reduced action potential backpropagation into dendrites, impairing synaptic plasticity and synaptic stability, even when NaV1.2 expression was disrupted late in development. Furthermore, we identified behavioral impairments in learning and sociability, paralleling observations in children with SCN2A loss. These results reveal a novel dendritic function for NaV1.2, providing insight into cellular mechanisms likely underlying circuit and behavioral dysfunction in ASD.
Socially regulated estrogen in an eavesdropping brood parasite
Authors: Lynch Kathleen S. , Azieva Gulnoza , Pellicano Anthony 
Published: July 2018

AbstractSocial regulation of reproductive hormones is a means by which conspecific males and females orchestrate successful reproductive efforts. There is variation, however, in the range of social cues that will initiate a hormone response in the receiver of social signals. We investigate whether social cues modify activity within the hypothalamic-pituitary-gonadal (HPG) axis and the specificity of this response in a social parasite that is known to eavesdrop on the communication signals of other species: the brown-headed cowbird (Molothrus ater). Brown-headed cowbirds are obligate brood parasites that do not build nests or care for their own young. Instead, obligate brood parasites always leave their eggs in the nest of a host species thereby receiving the benefits of parental care toward offspring without paying any of the costs. Thus, social parasites must coordinate their breeding attempts with conspecifics as well as potential heterospecific hosts and therefore, social parasites such as cowbirds rely on the communication signals of host species to help locate nests to parasitize during the breeding season. Here, we explore whether the vocal signals of potential host species can also be used as a social cue that modifies the HPG axis of female brown-headed cowbirds. Results reveal that both conspecific and heterospecific song-exposed females exhibit significantly greater circulating estradiol concentrations as compared to silence-exposed females. While conspecific song induces the greatest elevation in circulating estradiol, there is no significant difference in circulating estradiol levels in females exposed to either conspecific or heterospecific songs. This pattern suggests both song types are effective at evoking a reproductive physiological response. On the other hand, circulating progesterone concentrations did not differ among the song- and silence-exposed groups nor did the size of the female’s ovarian follicles. These results indicate that heterospecific vocal communication signals can effectively be used as a social cue that simultaneously provides necessary information regarding breeding status of hosts and modifies breeding condition of the eavesdropper.HighlightsBrood parasites may coordinate reproductive attempts with potential hosts.Therefore, parasites eavesdrop on other species, which helps them find nests.Vocal signals from conspecific and heterospecifics elevate estrogen in parasites.Hearing potential host songs may enhance reproductive hormones in brood parasites.
Empathy, closeness, and distance in non-profit accountability
Authors: Costa Ericka , Pesci Caterina , Andreaus Michele , Taufer Emanuele 
Published: July 2018

PurposeDrawing on the phenomenological concepts of “empathy” and “communal emotions” developed by Edith Stein (1917, 1922), the purpose of this paper is to discuss the co-existence both of the legitimacy and accountability perspectives in voluntarily delivered social and environmental reporting (SER), based on different “levels of empathy” towards different stakeholders.Design/methodology/approachThe paper adopts an interpretive research design, drawn from Stein’s concept of empathy by using a mixed-method approach. A manual content analysis was performed on 393 cooperative banks’ (CB) social and environmental reports from 2005 to 2013 in Italy, and 14 semi-structured interviews.FindingsThe results show that CBs voluntarily disclose information in different ways to different stakeholders. According to Stein, the phenomenological concept of empathy, and its understanding within institutions, allows us to interpret these multiple perspectives within a single social and environmental report. Therefore, when the process of acquiring knowledge in the CB–stakeholder relationship is complete and mentalised (level 3, re-enactive empathy), the SER holds high informative power, consistent with the accountability perspective; on the contrary, when this process is peripheral and perceptional (level 1, basic empathy), the SER tends to provide more self-assessment information, attempting to portray the bank in a positive light, which is consistent with the legitimacy perspective.Originality/valueThe concept of empathy introduced in this paper can assist in interpreting the interactions between an organisation and different stakeholders within the same social and environmental report. Moreover, the approach adopted in this paper considers different stakeholders simultaneously, thus responding to previous concerns regarding the lack of focus on multiple stakeholders.
Does FDI moderate the role of public R&D in accelerating agricultural production in Africa?
Authors: Adom Philip Kofi , Djahini-Afawoubo Dosse Mawussi , Mustapha Saidi Atanda , Fankem Stephane Gandjon , Rifkatu Nghargbu 
Published: July 2018

PurposeThe agriculture sector in Africa is a major employer, but production levels have fallen short of demand. To match future demand, public investment in research and development (R&D) is required. The purpose of this paper is to investigate how foreign direct investments (FDIs) moderate the effects of public R&D on Africa’s agricultural production.Design/methodology/approachThis study estimates an unbalanced panel fixed effect model that consists of 28 African countries covering the period 1980–2014.FindingsPublic R&D increases production in the agriculture sector, however, the effects reverse after ten years. Though FDIs have direct positive effects on production, indirectly, it reduces the productivity potential of public R&D due to the possible dependency syndrome associated with FDIs. Traditional inputs like land, capital, and labour and good political institutions positively drive production, but adverse changes in the weather reduce production.Practical implicationsThere should be a frequent update of R&D and improvement in maintenance culture. FDIs should be seen as complementary efforts, and not as substitute efforts to domestic investment efforts in R&D.Originality/valueInsufficient domestic investment has increased the dependence on FDIs. In this regard, FDIs effect on production could be tricky since it increases the volatility in agricultural R&D. This paper contributes to the literature by examining how FDIs moderate the effects of public R&D on output.