bluuebunny/crossref_metadata_2025_split huggingface dataset:
Endothelial and non-endothelial responses to estrogen excess during development lead to vascular malformations
Authors: Parajes Silvia , Ramas Sophie , Stainier Didier Y.R. 
Published: May 2018

ABSTRACTExcess estrogen signaling is associated with vascular malformations and pathologic angiogenesis, as well as tumor progression and metastasis. Yet, how dysregulated estrogen signaling impacts vascular morphogenesis in vivo remains elusive. Here we use live imaging of zebrafish embryos to determine the effects of excess estrogen signaling on the developing vasculature. We find that excess estrogens during development induce intersegmental vessel defects, endothelial cell-cell disconnections, and a shortening of the circulatory loop due to arterial-venous segregation defects. Whole-mount in situ hybridization and qPCR analyses reveal that excess estrogens negatively regulate Sonic hedgehog (Hh)/Vegf/Notch signaling. Activation of Hh signaling with SAG partially rescues the estrogen-induced vascular defects. Similarly, increased vegfaa bioavailability, using flt1/vegfr1 mutants or embryos overexpressing vegfaa165, also partially rescues the estrogen-induced vascular defects. We further find that excess estrogens promote aberrant endothelial cell (EC) migration, possibly as a result of increased PI3K and Rho GTPase signaling. Using estrogen receptor mutants and pharmacological studies, we show that Esr1 and the G-protein coupled estrogen receptor (Gper1) are the main receptors driving the estrogen-induced vascular defects. Mosaic overexpression of gper1 in ECs promotes vascular disconnections and aberrant migration, whereas no overt vascular defects were observed in mosaic embryos overexpressing wild-type or constitutively active nuclear estrogen receptors in their ECs. In summary, developmental estrogen excess leads to a mispatterning of the forming vasculature. Gper1 can act cell-autonomously in ECs to cause disconnections and aberrant migration, whilst Esr signaling predominantly downregulates Hh/Vegf/Notch signaling leading to impaired angiogenesis and defective arterial-venous segregation.Subject codes: angiogenesis, animal models of human disease, mechanisms, vascular biology.
Oculomotor capture reveals trial-by-trial neural correlates of attentional guidance by contents of visual working memory
Authors: Beck Valerie M. , Vickery Timothy J. 
Published: May 2018

AbstractEvidence from attentional and oculomotor capture, contingent capture, and other paradigms suggests that mechanisms supporting human visual working memory (VWM) and visual attention are intertwined. Features held in VWM bias guidance toward matching items even when those features are task irrelevant. However, the neural basis of this interaction is underspecified. Prior examinations using fMRI have primarily relied on coarse comparisons across experimental conditions that produce varying amounts of capture. To examine the neural dynamics of attentional capture on a trial-by-trial basis, we applied an oculomotor paradigm that produced discrete measures of capture. On each trial, subjects were shown a memory item, followed by a blank retention interval, then a saccade target that appeared to the left or right. On some trials, an irrelevant distractor appeared above or below fixation. Once the saccade target was fixated, subjects completed a forced-choice memory test. Critically, either the target or distractor could match the feature held in VWM. Although task irrelevant, this manipulation produced differences in behavior: participants were more likely to saccade first to an irrelevant VWM-matching distractor compared with a non-matching distractor – providing a discrete measure of capture. We replicated this finding while recording eye movements and scanning participants’ brains using fMRI. To examine the neural basis of oculomotor capture, we separately modeled the retention interval for capture and non-capture trials within the distractor-match condition. We found that frontal activity, including anterior cingulate cortex and superior frontal gyrus regions, differentially predicted subsequent oculomotor capture by a memory-matching distractor. Other regions previously implicated as involved in attentional capture by VWM-matching items showed no differential activity across capture and no-capture trials, even at a liberal threshold. Our findings demonstrate the power of trial-by-trial analyses of oculomotor capture as a means to examine the underlying relationship between VWM and attentional guidance systems.
A community-level investigation of the yellow fever virus outbreak in South Omo Zone, South-West Ethiopia, 2012–2014
Authors: Mulchandani Ranya , Massebo Fekadu , Bocho Fekadu , Jeffries Claire L , Walker Thomas , Messenger Louisa A 
Published: May 2018

AbstractBackgroundA yellow fever (YF) outbreak occurred in South Omo Zone, Ethiopia in 2012-2014. This study aimed to analyse historical epidemiological data, to assess the risk for future YF outbreaks through entomological surveillance, including mosquito species identification and molecular screening for arboviruses, and finally to determine the knowledge, attitudes and current preventative practices within the affected communities.Methodology/Principal FindingsFrom October 2012 to March 2014, 165 cases and 62 deaths were reported, principally in rural areas of South Ari region (83.6%), south-west Ethiopia. The majority of patients were 15-44 years old (74.5%) and most case deaths were males (76%). Between June and August 2017, 688 containers were sampled from across 177 households to identify key breeding sites forAedesmosquitoes.Ensete ventricosum(“false banana”) was identified as the primary natural breeding site, and clay pots outside the home as the most productive artificial breeding site. Entomological risk indices from the majority of sites were classified as “high risk” for future outbreaks under current World Health Organization criteria. Adult trapping resulted in the identification of members of theAedes simpsonicomplex in and around households. Screening of adult females revealed no detection of yellow fever virus (YFV) or other arboviruses. 88% of 177 participants had heard of YF, however many participants easily confused transmission and symptoms of YF with malaria, which is also endemic in the area.Conclusions/SignificanceStudy results emphasise the need for further entomological studies to improve our understanding of local vector species and transmission dynamics. Disease surveillance systems and in-country laboratory capacity also need to be strengthened to facilitate more rapid responses to future YF outbreaks.Author SummaryDespite the availability of a highly effective vaccine, yellow fever virus (YFV) remains an important public health problem across Africa and South America due to its high case-fatality rate. This study aimed to assess and reduce the risk for future outbreaks. During this study, historical data analysis was conducted to understand the epidemiology of the recent outbreak in 2012-2014. Entomological surveillance was also carried out, including both mosquito species identification and molecular screening for arboviruses, as well as a household survey to understand the knowledge and attitudes towards yellow fever (YF) within the affected areas and to assess community-level practices for YF prevention. We found a high abundance ofAedes simpsonicomplex in the context of low vaccination coverage. Community knowledge and practice levels were low for reducing potential breeding sites, highlighting the need for increased dissemination of information to community members on how to reduce their risk of exposure to mosquito vectors of arboviruses.
Examining food intake and eating out of home patterns among university students
Authors: Llanaj Erand , Àdàny Róza , Lachat Carl , D’Haese Marijke 
Published: May 2018

AbstractEating out of home (OH) is increasingly popular in Balkan countries, among them Albania. To date there is only anecdotal evidence regarding nutritional quality of food consumed OH and the contribution to diet. This study assessed intake of foods and drinks consumed OH and at home (AH), as well as their nutritional contribution to the daily diet of university students in Tirana, Albania. Using a single day Automated Multiple Pass Method (AMPM) 24-hour dietary recall, we examined food intake among 289 students aged 18-24 years old, from three major universities in Albania. Contribution of eating OH to total energy intake per day, as well as to daily consumption of macronutrients by eating OH intensity tertiles were assessed. Foods and drinks consumed OH contributed 46.9% [95%CI:41.4-52.8] of total daily energy intake, representing, on average, 1169.1kcal [95%CI:1088.3-1249.9]. Sweets, soft drinks and meat products were more frequently consumed OH, while fruits and vegetables consumption was extremely low. The average quantity of sugars and dietary fats per day was higher AH, 76.9g [95%CI:70.3-83.5] and 173.7g [95%CI:163.2-184.2] respectively, compared to OH, 33.7g [95%CI:30.4-37.0] and 142.0g [95%CI:131.5-152.5] respectively. Dietary composition of AH intake was richer in sugars, total fats and proteins, while OH intake was richer in saturated fats. The overall diet appeared unhealthy, when nutrients were assessed as energy percentage against WHO proposed nutrient standards for sugar and saturated fats. Eating OH, even though was associated with lower fruits and vegetables intake, was not clearly associated with poor diet quality, as AH foods were also characterized by increased saturated fats and sugars intake as energy percentage. This study provides data on the first assessment of current dietary patterns of the studied population and can be used as baseline for designing and conducting future studies and interventions targeting malnutrition in all its forms.
Human genomics of acute liver failure due to hepatitis B virus infection: an exome sequencing study in liver transplant recipients
Authors: Asgari Samira , Chaturvedi Nimisha , Scepanovic Petar , Hammer Christian , Semmo Nasser , Giostra Emiliano , Müllhaupt Beat , Angus Peter , Thompson Alexander J , Moradpour Darius , Fellay Jacques 
Published: May 2018

AbstractAcute liver failure (ALF) or fulminant hepatitis is a rare, yet severe outcome of infection with hepatitis B virus (HBV) that carries a high mortality rate. The occurrence of a life-threatening condition upon infection with a prevalent virus in individuals without known risk factors is suggestive of pathogen-specific immune dysregulation. In the absence of established differences in HBV virulence, we hypothesized that ALF upon primary infection with HBV could be due to rare deleterious variants in the human genome. To search for such variants, we performed exome sequencing in 21 previously healthy adults who required liver transplantation upon fulminant HBV infection and 172 controls that were positive for anti-HBc and anti-HBs antibodies but had no clinical history of jaundice or liver disease. After a series of hypothesis-driven filtering steps, we searched for putatively pathogenic variants that were significantly associated with case-control status. We did not find any causal variant or gene, a result that does not support the hypothesis of a shared monogenic basis for human susceptibility to HBV-related ALF in adults. This study represents a first attempt at deciphering the human genetic contribution to the most severe clinical presentation of acute HBV infection in previously healthy individuals.Author SummaryInfection with hepatitis B virus (HBV) is very common and causes a variety of liver diseases including acute and chronic hepatitis, cirrhosis and liver carcinoma. Acute HBV infection is often asymptomatic, still about 1% of newly infected people develop a rapid and severe disease known as acute liver failure or fulminant hepatitis. Acute liver failure has a high mortality rate and is an indication for urgent liver transplantation. It is not clear why some people, who are otherwise healthy, develop such severe symptoms upon infection with a common pathogen. Here, we hypothesized that rare DNA variants in the human genome could contribute to this unusual susceptibility. We sequenced the exome (i.e. the regions of the genome that encode the proteins) of 21 previously healthy adults who required liver transplantation upon fulminant HBV infection and searched for rare genetic variants that could explain the clinical presentation. We did not identify any variant that could be convincingly linked to the extreme susceptibility to HBV observed in the study participants. This suggests that HBV-induced acute liver failure is more likely to result from the combined influence of multiple genetic and environmental factors.
The protozoanTrichomonas vaginalistargets bacteria with laterally-acquired NlpC/P60 peptidoglycan hydrolases
Authors: Pinheiro Jully , Biboy Jacob , Vollmer Waldemar , Hirt Robert P. , Keown Jeremy R. , Artuyants Anastasiia , Goldstone David C. , Simoes-Barbosa Augusto 
Published: May 2018

AbstractTrichomonas vaginalisis a human eukaryotic pathogen and the causative agent of trichomoniasis, the most prevalent non-viral sexually transmitted infection worldwide. This extracellular protozoan parasite is intimately associated with the human vaginal mucosa and microbiota but key aspects of the complex interactions between the parasite and the vaginal bacteria remain elusive. We report thatT. vaginalishas acquired, by lateral gene transfer from bacteria, genes encoding peptidoglycan hydrolases of the NlpC/P60 family. Two of theT. vaginalisenzymes were active against bacterial peptidoglycan, retaining the active site fold and specificity as DL-endopeptidases. The endogenous NlpC/P60 genes are transcriptionally up regulated inT. vaginaliswhen in the presence of bacteria. The over-expression of an exogenous copy produces a remarkable phenotype where the parasite is capable of competing out bacteria from mixed cultures, consistent with the biochemical activity of the enzymein vitro. Our study highlights the relevance of the interactions of this eukaryotic pathogen with bacteria, a poorly understood aspect on the biology of this important human parasite.Author summaryTrichomonas vaginalisis a protozoan parasite that causes a very common sexually transmitted disease known as trichomoniasis. This extracellular parasite resides in the vagina where it is in close association with the mucosa and the local microbiota. Very little is known about the nature of the parasite-bacteria interactions. Here, we report that this parasite had acquired genes from bacteria which retained their original function producing active enzymes capable of degrading peptidoglycan, a polymer that is chemically unique to the cell envelope of bacteria. Our results indicate that these enzymes help the parasite compete out bacteria in mixed cultures. These observations suggest that these enzymes may be critical for the parasite to establish infection in the vagina, a body site that is densely colonised with bacteria. Our study further highlights the importance of understanding the interactions between pathogens and microbiota, as the outcomes of these interactions are increasingly understood to have important implications on health and disease.
Robust associative learning is sufficient to explain structural and dynamical properties of local cortical circuits
Authors: Zhang Danke , Zhang Chi , Stepanyants Armen 
Published: May 2018

ABSTRACTThe ability of neural networks to associate successive states of network activity lies at the basis of many cognitive functions. Hence, we hypothesized that many ubiquitous structural and dynamical properties of local cortical networks result from associative learning. To test this hypothesis, we trained recurrent networks of excitatory and inhibitory neurons on memory sequences of varying lengths and compared network properties to those observed experimentally. We show that when the network is robustly loaded with near-maximum amount of associations it can support, it develops properties that are consistent with the observed probabilities of excitatory and inhibitory connections, shapes of connection weight distributions, overrepresentations of specific 3-neuron motifs, distributions of connection numbers in clusters of 3–8 neurons, sustained, irregular, and asynchronous firing activity, and balance of excitation and inhibition. What is more, memories loaded into the network can be retrieved even in the presence of noise comparable to the baseline variations in the postsynaptic potential. Confluence of these results suggests that many structural and dynamical properties of local cortical networks are simply a byproduct of associative learning.
DOT1L suppresses nuclear RNAi originating from enhancer elements in Caenorhabditis elegans
Authors: Esse Ruben , Gushchanskaia Ekaterina , Lord Avery , Grishok Alla 
Published: May 2018

ABSTRACTMethylation of histone H3 on lysine 79 (H3K79) by DOT1L is associated with actively transcribed genes. Earlier, we described that DOT-1.1, the Caenorhabditis elegans DOT1L homologue, cooperates with the chromatin-binding protein ZFP-1 (AF10 homologue) to negatively modulate transcription of highly and widely expressed target genes. Also, reduction in ZFP-1 levels has long been associated with lower efficiency of RNA interference (RNAi) triggered by exogenous double-stranded RNA (dsRNA), but the reason for this is not clear. Here, we demonstrate that DOT1L suppresses bidirectional transcription, including that producing enhancer RNAs, thereby preventing dsRNA formation and ectopic RNAi. This ectopic elevation of endogenous dsRNA may engage the Dicer complex and, therefore, limit efficiency of exogenous RNAi. Our insight provides a novel perspective on the underlying mechanisms of DOT1L function in development, neural activity, and cancer.
Innate potential of random genetic oligomer pools for recombination
Authors: Mutschler Hannes , Taylor Alexander I. , Lightowlers Alice , Houlihan Gillian , Abramov Mikhail , Herdewijn Piet , Holliger Philipp 
Published: May 2018

AbstractThe spontaneous emergence of function from prebiotic pools of informational polymers is a central conjecture of current origin of life scenarios. However, the innate functional capacity of random genetic polymer pools is unknown. Here, we have examined the ab initio activity of random and semi-random eicosamer pools of RNA, DNA and the unnatural genetic polymers ANA (arabino-), HNA (hexitol-) and AtNA (altritol-nucleic acids) with respect to a simple functional test: the capacity for intermolecular ligation and recombination. While DNA, ANA and HNA pools proved inert, naïve RNA and AtNA pools displayed diverse modes of intermolecular recombination in eutectic ice phases. Recombination appears linked to the vicinal ring cis-diol shared by RNA and AtNA. Thus, the chemical configuration that renders both susceptible to hydrolysis also enables substantial spontaneous intrapool recombination in the absence of activation chemistry with a concomitant increase in the compositional and structural complexity of recombined pools.
Chronic in vivo optogenetic stimulation modulates neuronal excitability, spine morphology and Hebbian plasticity in the mouse hippocampus
Authors: Moulin Thiago C. , Petiz Lyvia L. , Rayêe Danielle , Winne Jessica , Maia Roberto G. , Cruz Rafael V. Lima da , Amaral Olavo B. , Leão Richardson N. 
Published: May 2018

AbstractProlonged increases in excitation can trigger cell-wide homeostatic responses in neurons, altering membrane channels, promoting morphological changes and ultimately reducing synaptic weights. However, how synaptic downscaling interacts with classical forms of Hebbian plasticity is still unclear. In this study, we investigated whether chronic optogenetic stimulation of hippocampus CA1 pyramidal neurons in freely-moving mice could (a) cause morphological changes reminiscent of homeostatic scaling, (b) modulate synaptic currents that might compensate for chronic excitation, and (c) lead to alterations in Hebbian plasticity. After 24 h of stimulation with 15-ms blue light pulses every 90 s, dendritic spine density and area were reduced in the CA1 region of mice expressing channelrhodopsin-2 (ChR2) when compared to controls. This protocol also reduced the amplitude of mEPSCs for both the AMPA and NMDA components in ex vivo slices obtained from ChR2-expressing mice immediately after the end of stimulation. Lastly, chronic stimulation impaired the induction of LTP and facilitated that of LTD in these slices. Our results indicate that neuronal responses to prolonged network excitation can modulate subsequent Hebbian plasticity in the hippocampus.
High-resolution ISR amplicon sequencing reveals personalized oral microbiome
Authors: Mukherjee Chiranjit , Beall Clifford J. , Griffen Ann L. , Leys Eugene J. 
Published: May 2018

AbstractBackground:Sequencing of the 16S rRNA gene has been the standard for studying the composition of microbial communities. While it allows identification of bacteria at the level of species, it does not usually provide sufficient information to resolve at the sub-species level. Species-level resolution is not adequate for studies of transmission or stability, or for exploring subspecies variation in disease association. Current approaches using whole metagenome shotgun sequencing require very high coverage that can be cost-prohibitive and computationally challenging for diverse communities. Thus there is a need for high-resolution, yet cost-effective, high-throughput methods for characterizing microbial communities.Results:Significant improvement in resolution for amplicon-based bacterial community analysis was achieved by combining amplicon sequencing of a high-diversity marker gene, the ribosomal operon ISR, with a probabilistic error modeling algorithm, DADA2. The resolving power of this new approach was compared to that of both standard and high-resolution 16S-based approaches using a set of longitudinal subgingival plaque samples. The ISR strategy achieved a 5.2-fold increase in community richness compared to reference-based 16S rRNA gene analysis, and showed 100% accuracy in predicting the correct source of a clinical sample. Individuals’ microbial communities were highly personalized, and although they exhibited some drift in membership and levels over time, that difference was always smaller than the differences between any two subjects, even after one year. The construction of an ISR database from publicly available genomic sequences allowed us to explore genomic variationwithinspecies, resulting in the identification of multiple variants of the ISR for most species.Conclusions:The ISR approach resulted in significantly improved resolution of communities, and revealed a highly personalized, stable human oral microbiota. Multiple ISR types were observed for all species examined, demonstrating a high level of subspecies variation in the oral microbiota. The approach is high-throughput, high-resolution yet cost-effective, allowing subspecies-level community fingerprinting at a cost comparable to that of 16S rRNA gene amplicon sequencing. It will be useful for a range of applications that require high-resolution identification of organisms, including microbial tracking, community fingerprinting, and potentially for identification of virulence-associated strains.