bluuebunny/crossref_metadata_2025 huggingface dataset:
Enzymatic browning reaction of apple juices prepared using a blender and a low-speed masticating household juicer
Authors: Park Shin-Young , Kang Tae-Min , Kim Min-Ju , Kim Myo-Jeong
Published: August 2018

The aim of this study was to investigate the effect of juicer type (blender or LSM household juicer) on the browning reaction of apple juice and evaluate the remaining antioxidant activity in the juice. The blender apple juice showed a darker brown color and 4.5 times higher PPO activity than LSM apple juice. This result suggested that the blender caused severer damage to plastids in cells leading to leakage of PPO into the juice than the LSM juicer. The total polyphenol and flavonoid content of LSM apple juice was approximately 2 times higher than that of blender apple juice because polyphenols and flavonoids can be used as substrates by PPO. The antioxidant activity of LSM juice was higher than that of blender juice. Together, these results suggested that the LSM juicer is superior to the blender for preparation of fresh apple juices due to the minimization of enzymatic oxidation reactions.

Abbreviations: LSM: low-speed masticating; PPO: polyphenol oxidase; ABTS: 2,2ʹ-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid); DPPH: 2,2-diphenyl-1-picrylhydrazyl
Augmentation of dietary glucosylceramide hydrolysis by the novel bacterium Glucerabacter canisensis NATH-2371T
Authors: Kawata Misho , Suzuki Masato , Akutsu Shoko , Kawahara Natsuki , Tsukamoto Ami , Nobukawa Shohei , Isozaki Ryohei , Yuyama Seika , Asanuma Narito
Published: August 2018

The purpose of this study was to evaluate the effects of intragastrical administration of Glucerabacter canisensis NATH-2371T on glucosylceramide (GluCer) digestion in mice. Although G. canisensis was unable to utilize starch and cellulose, coculture of G. canisensis with mouse fecal bacteria greatly increased GluCer hydrolysis in polysaccharide medium, indicating that G. canisensis grew in competition with other intestinal bacteria. Although most of the administered G. canisensis cells were detected in feces, some cells were present in the colorectum contents, which had GluCer-hydrolyzing activity. These results indicate that G. canisensis can viably transit through the mouse gut. Administration of G. canisensis to mice fed diets supplemented with GluCer or GluCer-containing foods significantly enhanced GluCer hydrolysis. Since G. canisensis did not show acute toxicity, it may be useful as a probiotic to augment GluCer hydrolysis in the large intestine.

Abbreviations: GluCer: glucosylceramide; KPi: potassium phosphate buffer; C-M: chloroform-methanol
Effect of Aurea Helianthus stem extract on anti-melanogenesis
Authors: Kim Yehyang , Lee Sohun , Ryu Ji Hye , Yoon Kee Dong , Shin Song Seok
Published: August 2018

Aurea Helianthus (AH), also known as wild confederate rose or golden sunflower, is a curative herb. It has been used as a medicinal material in China due to its anti-inflammatory, immune regulatory, and anti-oxidant activities. However, its melanogenic effect on skin has not been sufficiently investigated. In this study, we tested whether AH has melanogenic inhibitory activities for the development of effective skin whitening agent. The extract showed inhibition of melanin synthesis and reduced the oxidation of 3, 4-dihydroxyphenilalanine (DOPA) to o-dopaquinone. Additionally, AH downregulated the levels of microphthalmia-associated transcription factor (MITF), tyrosinase and tyrosinase related proteins (TRPs), suggesting that AH has inhibitory effects on melanogenesis. Analysis of the components of AH showed that it contained paprazine and trans-N-feruloyltyramine (FA). We confirmed that the effect of AH resulted from paprazine and FA. Therefore, AH might have potential as an effective candidate for skin whitening.
Determination of the traverse force in friction stir welding with different tool pin profiles
Authors: Su Hao , Wu Chuansong
Published: August 2018

A methodology is developed for the estimation of the traverse force in friction stir welding (FSW) for various pin profiles by combining the results of numerical modelling and experimental monitoring. The effect of pin profiles on the traverse force is evaluated by introducing a modified ratio of the plastic deformation zone, which is obtained by numerical modelling. The formula is validated with the experimental data in the literature and indicates that the traverse force decreases exponentially with increasing ratio of the plastic deformation zone. The proposed methodology provides a concise approach for the estimation of the traverse force for various pin profiles in FSW and can be adopted for the design and assessment of the FSW tool.
A Case-Control Study to Identify Community Venues Associated with Genetically-clustered, Multidrug-resistant Tuberculosis Disease in Lima, Peru
Authors: Bui David P , Oren Eyal , Roe Denise J , Brown Heidi E , Harris Robin B , Knight Gwenan M , Gilman Robert H , Grandjean Louis
Published: August 2018

Background

The majority of tuberculosis transmission occurs in community settings. Our primary aim in this study was to assess the association between exposure to community venues and multidrug-resistant (MDR) tuberculosis. Our secondary aim was to describe the social networks of MDR tuberculosis cases and controls.

Methods

We recruited laboratory-confirmed MDR tuberculosis cases and community controls that were matched on age and sex. Whole-genome sequencing was used to identify genetically clustered cases. Venue tracing interviews (nonblinded) were conducted to enumerate community venues frequented by participants. Logistic regression was used to assess the association between MDR tuberculosis and person-time spent in community venues. A location-based social network was constructed, with respondents connected if they reported frequenting the same venue, and an exponential random graph model (ERGM) was fitted to model the network.

Results

We enrolled 59 cases and 65 controls. Participants reported 729 unique venues. The mean number of venues reported was similar in both groups (P = .92). Person-time in healthcare venues (adjusted odds ratio [aOR] = 1.67, P = .01), schools (aOR = 1.53, P < .01), and transportation venues (aOR = 1.25, P = .03) was associated with MDR tuberculosis. Healthcare venues, markets, cinemas, and transportation venues were commonly shared among clustered cases. The ERGM indicated significant community segregation between cases and controls. Case networks were more densely connected.

Conclusions

Exposure to healthcare venues, schools, and transportation venues was associated with MDR tuberculosis. Intervention across the segregated network of case venues may be necessary to effectively stem transmission.
Smoking and HIV in Sub-Saharan Africa: A 25-Country Analysis of the Demographic Health Surveys
Authors: Murphy John D , Liu Benmei , Parascandola Mark
Published: August 2018

Background

Having HIV/AIDS has been associated with a higher prevalence of smoking. Moreover, evidence suggests that people with HIV/AIDS who smoke have poorer treatment and survival outcomes. The HIV–smoking relationship is understudied in sub-Saharan Africa, where tobacco use patterns and HIV prevalence differ greatly from other world regions.

Methods

Cross-sectional data from the Demographic Health Surveys and AIDS Indicator Surveys, representing 25 sub-Saharan African countries, were pooled for analysis (n = 286850). The association between cigarette smoking and HIV status was analyzed through hierarchical logistic regression models. This study also examined the relationship between smokeless tobacco (SLT) use and HIV status.

Results

Smoking prevalence was significantly higher among men who had HIV/AIDS than among men who did not (25.90% vs 16.09%; p < .0001), as was smoking prevalence among women who had HIV/AIDS compared with women who did not (1.15% vs 0.73%; p < .001). Multivariate logistic regression revealed that the odds of smoking among people who had HIV/AIDS was 1.12 times greater than among people who did not when adjusting for socioeconomic, demographic, and sexual risk factors (adjusted OR = 1.12, 95% CI = 1.04% to 1.21%; p < .001). Similarly, multivariate logistic regression revealed that HIV-positive individuals were 34% more likely to use SLT than HIV-negative individuals (adjusted OR = 1.34, 95% CI = 1.17% to 1.53%).

Conclusion

Having HIV was associated with a greater likelihood of smoking cigarettes as well as with using SLT in sub-Saharan Africa. These tobacco use modalities were also associated with male sex and lower socioeconomic status.

Implications

This study shows that in sub-Saharan Africa, as in more studied world regions, having HIV/AIDS is associated with a higher likelihood of smoking cigarettes when adjusting for demographic, socioeconomic, and sexual risk factors. This study also supports the literature stating that cigarette smoking is inversely associated with socioeconomic status, as evidenced by higher smoking prevalence among poorer individuals, less educated individuals, and manual and agricultural laborers.
Employment and occupational outcomes following adolescent-onset mental illness: analysis of a nationally representative French cohort
Authors: Witt Katrina , Milner Allison , Chastang Jean-François , LaMontagne Anthony D , Niedhammer Isabelle
Published: August 2018

Background

There has been little work into the relative effects of adolescent-onset, as compared to lifetime, mental illness on employment, income and occupational outcomes in adulthood.

Methods

Using data from the Santé et Itinéraire Professionnel Survey, a nationally representative survey of 13 648 French working-age people to investigate prospective associations between self-reported mental illness and employment, income and occupational outcomes. We further investigated whether these outcomes would differ for those reporting an onset of mental illness prior to 18 years of age.

Results

Adolescent-onset mental illness was associated with poorer employment outcomes, significantly increased risk of employment in low-skilled occupations, as well as reduced monthly wage earnings.

Conclusions

Results extend understandings of the risks of adolescent-onset mental illness on employment and occupational outcomes and suggest that vocational recovery services should take these factors into account when designing support services for adolescents with mental health problems, particularly for males.
Environments with a high probability of incompatible crosses do not select for mate avoidance in spider mites
Authors: Rodrigues Leonor R , Zélé Flore , Santos Inês , Magalhães Sara
Published: August 2018

Arthropods are often infected withWolbachiainducing cytoplasmic incompatibility (CI), whereby crosses between uninfected females and infected males yield unviable fertilized offspring. Although uninfected females benefit from avoiding mating withWolbachia-infected males, this behaviour is not present in all host species. Here we measured the prevalence of this behaviour across populations of the spider miteTetranychus urticae. Females from five populations originally fully infected withWolbachiashowed no preference, possibly because they did not face the choice between compatible and incompatible mates in their environment. Hence, to determine whether this behaviour could be selected in populations with intermediateWolbachiainfection frequency, we performed 15 generations of experimental evolution of spider-mite populations under i) fullWolbachiainfection, ii) no infection, or iii) mixed infection. In the latter selection regime, where uninfected females were exposed to infected and uninfected males at every generation, mating duration increased relative to the uninfected regime, suggesting the presence of genetic variation for mating traits. However, mate choice did not evolve. Together, these results show that CI-inducingWolbachiaalone does not necessarily lead to the evolution of pre-copulatory strategies in uninfected hosts, even at intermediate infection frequency.
MicroRNA regulation of BMP signaling; cross-talk between endothelium and vascular smooth muscle cells
Authors: Watterston Charlene , Zeng Lei , Onabadejo Abidemi , Childs Sarah J
Published: August 2018

Vascular smooth muscle cells (vSMC) are essential to the integrity of blood vessels, and therefore an attractive target of therapeutics aimed at improving vascular function. Smooth muscle cells are one of the few cell types that maintain plasticity and can switch phenotypes from differentiated (contractile) to de-differentiated (synthetic) and vice versa. As small regulatory transcripts, miRNAs act as genetic ‘fine tuners’ of posttranscriptional events and can act as genetic switches promoting phenotypic switching. The microRNAmiR26atargets the BMP signalling effector,smad1. We show that loss ofmiR26leads to hemorrhage (a loss of vascular stability)in vivo, suggesting altered vascular differentiation. Reduction inmiR26alevels increasessmad1mRNA and phospho-Smad1 (pSmad1) levels. We show that increasing BMP signalling by overexpression ofsmad1also leads to hemorrhage and that normalization of Smad1 levels through double knockdown ofmiR26andsmad1rescues hemorrhage suggesting a direct relationship betweenmiR26andsmad1and vascular stability. Using a BMP genetic reporter and pSmad1 staining we show that the effect ofmiR26on vascular instability is non-autonomous; BMP signalling is active in embryonic endothelial cells, but not in smooth muscle cells. Nonetheless, increased BMP signalling due to loss ofmiR26results in an increase inacta2-expressing smooth muscle cell numbers and promotes a differentiated smooth muscle morphology. Taken together our data suggests thatmiR26modulates BMP signalling in endothelial cells and indirectly promotes a differentiated smooth muscle phenotype. Our data also suggests that crosstalk from BMP-responsive endothelium to smooth muscle is important for its differentiation.
Basalin: an evolutionary unconstrained protein revealed via a conserved role in basal plate function
Authors: Dean Samuel , Moreira-Leite Flavia , Gull Keith
Published: August 2018

Most motile flagella have an axoneme that contains nine outer microtubule doublets and a central pair (CP) of microtubules. The CP is thought to coordinate the flagellar beat and defects in CP projections are associated with loss of motility and human disease. In most cilia, the CP nucleate near a ‘basal plate’ at the distal end of the transition zone (TZ). Here, we show that the trypanosome TZ protein ‘basalin’ is essential for building the basal plate, and its loss is associated with inefficient recruitment of CP assembly factors to the TZ, loss of the CP and flagellum paralysis. Guided by synteny, we identified highly divergent basalin orthologs in the genomes of related Leishmania species. Basalins are predicted to be highly unstructured, suggesting that they may act as ‘hubs’ facilitating many protein-protein interactions. This raises the general concept that proteins involved in cytoskeletal functions and apparently appearing organism-specific, may have highly divergent and cryptic orthologs in other species.
Widespread methane formation byCyanobacteriain aquatic and terrestrial ecosystems
Authors: Bižić-Ionescu M. , Klintzsch T. , Ionescu D. , Hindiyeh M. Y. , Günthel M. , Muro-Pastor A.M. , Eckert W. , Keppler F. , Grossart H-P
Published: August 2018

Evidence is accumulating to challenge the paradigm that biogenic methanogenesis, traditionally considered a strictly anerobic process, is exclusive toArchaea. Here we demonstrate that Cyanobacteria living in marine, freshwater and terrestrial environments produce methane at substantial rates under light and dark oxic and anoxic conditions, forming a link between light driven primary productivity and methane production in globally relevant group of phototrophs. Biogenic methane production was enhanced during oxygenic photosynthesis and directly attributed to the cyanobacteria by applying stable isotope labelling techniques. We suggest that formation of methane byCyanobacteriamay contribute to methane accumulation in oxygen-saturated surface waters of marine and freshwater ecosystems. Moreover, in these environments, cyanobacterial blooms already do, and might further occur more frequently during future global warming and thus have a direct feedback on climate change. We further highlight that cyanobacterial methane production not only affects recent and future global methane budgets, but also has implications for inferences on Earth’s methane budget for the last 3.5 billion years, when this phylum is thought to have first evolved.
Incorporating in-source fragment information improves metabolite identification accuracy in untargeted LC-MS datasets
Authors: Seitzer Phillip M. , Searle Brian C.
Published: August 2018

[ABSTRACT]

In-source fragmentation occurs as a byproduct of electrospray ionization. We find that ions produced as a result of in-source fragmentation often match fragment ions produced during MS/MS fragmentation and we take advantage of this phenomenon in a novel algorithm to analyze LC-MS metabolomics datasets. Our approach organizes co-eluting MS1 features into a single peak group and then identifies in-source fragments among co-eluting features using MS/MS spectral libraries. We tested our approach using previously published data of verified metabolites, and compared the results to features detected by other mainstream metabolomics tools. Our results indicate that considering in-source fragment information as a part of the identification process increases annotation quality, allowing us to leverage MS/MS data in spectrum libraries even if MS/MS scans were not collected.
Structural basis of Toxoplasma gondii Perforin-Like Protein 1 membrane interaction and activity during egress
Authors: Guerra Alfredo J. , Zhang Ou , Bahr Constance M. E. , Huynh My-Hang , DelProposto James , Brown William C. , Wawrzak Zdzislaw , Koropatkin Nicole M. , Carruthers Vern B.
Published: August 2018

Intracellular pathogens must egress from the host cell to continue their infectious cycle. Apicomplexans are a phylum of intracellular protozoans that have evolved members of the membrane attack complex and perforin (MACPF) family of pore forming proteins to disrupt cellular membranes for traversing cells during tissue migration or egress from a replicative vacuole following intracellular reproduction. Previous work showed that the apicomplexan Toxoplasma gondii secretes a perforin-like protein (TgPLP1) that contains a C-terminal Domain (CTD) which is necessary for efficient parasite egress. However, the structural basis for CTD membrane binding and egress competency remained unknown. Here, we present evidence that TgPLP1 CTD prefers binding lipids that are abundant in the inner leaflet of the lipid bilayer. Additionally, solving the high-resolution crystal structure of the TgPLP1 APCβ domain within the CTD reveals an unusual double-layered β-prism fold that resembles only one other protein of known structure. Three direct repeat sequences comprise subdomains, with each constituting a wall of the β-prism fold. One subdomain features a protruding hydrophobic loop with an exposed tryptophan at its tip. Spectrophotometric measurements of intrinsic tryptophan fluorescence are consistent with insertion of the hydrophobic loop into a target membrane. Using CRISPR/Cas9 gene editing we show that parasite strains bearing mutations in the hydrophobic loop, including alanine substitution of the tip tryptophan, are equally deficient in egress as a strain lacking TgPLP1 altogether. Taken together our findings suggest a crucial role for the hydrophobic loop in anchoring TgPLP1 to the membrane to support its cytolytic activity and egress function.

Author Summary

Toxoplasma gondii has a complex life cycle that involves active invasion of the host cell, the formation of a replicative compartment, and egress from the replicative niche. T. gondii encodes a pore-forming protein, TgPLP1, that contains a C-terminal domain that is crucial for efficient exit from both the parasite containing vacuole and the host cell. However, the mechanism by which TgPLP1 recognizes and binds to the appropriate membrane is unclear. Here we use a combination of biochemistry, structural biology, and parasitology to identify the a preference of TgPLP1 for specific lipids and show that a loop within the structure of the C-terminal domain inserts into the membrane and is necessary for egress from the parasite containing vacuole. Our study sheds light into the determinants of membrane binding in TgPLP1 which may inform the overall mechanism of pore formation in similar systems
Regulation of tensile stress in response to external forces coordinates epithelial cell shape transitions with organ growth and elongation
Authors: Balaji Ramya , Weichselberger Vanessa , Classen Anne-Kathrin
Published: August 2018

The role of actomyosin contractility at epithelial adherens junctions has been extensively studied. However, little is known about how external forces are integrated to establish epithelial cell and organ shapein vivo. We use theDrosophilafollicle epithelium to investigate how tension at adherens junctions is regulated to integrate external forces arising from changes in germline size and shape. We find that overall tension in the epithelium decreases despite pronounced growth of enclosed germline cells, suggesting that the epithelium relaxes to accommodate growth. However, we find local differences in adherens junction tension correlate with apposition to germline nurse cells or the oocyte. We demonstrate that medial Myosin II coupled to corrugating adherens junctions resists nurse cell-derived forces and thus maintains apical surface areas and cuboidal cell shapes. Furthermore, medial reinforcement of the apical surface ensures cuboidal-to-columnar cell shape transitions and imposes circumferential constraints on nurse cells guiding organ elongation. Our study provides insight into how tension within an adherens junction network integrates growth of a neighbouring tissue, mediates cell shape transitions and channels growth into organ elongation.
PIRD: Pan immune repertoire database
Authors: Zhang Wei , Wang Longlong , Liu Ke , Wei Xiaofeng , Yang Kai , Du Wensi , Wang Shiyu , Guo Nannan , Ma Chuanchuan , Luo Lihua , Wu Jinghua , Lin Liya , Yang Fan , Gao Fei , Wang Xie , Li Tao , Zhang Ruifang , Saksena Nitin K. , Yang Huanming , Wang Jian , Fang Lin , Hou Yong , Xu Xun , Liu Xiao
Published: August 2018

Motivation

T and B cell receptors (TCRs and BCRs) play a pivotal role in the adaptive immune system by recognizing an enormous variety of external and internal antigens. Understanding these receptors is critical for exploring the process of immunoreaction and exploiting potential applications in immunotherapy and antibody drug design. Although a large number of samples have had their TCR and BCR repertoires sequenced using high-throughput sequencing in recent years, very few databases have been constructed to store these kinds of data. To resolve this issue, we developed a database.

Results

We developed a database, the Pan Immune Repertoire Database (PIRD), located in China National GeneBank (CNGBdb), to collect and store annotated TCR and BCR sequencing data, including fromHomo sapiensand other species. In addition to data storage, PIRD also provides functions of data visualisation and interactive online analysis. Additionally, a manually curated database of TCRs and BCRs targeting known antigens (TBAdb) was also deposited in PIRD.

Availability and Implementation

PIRD can be freely accessed athttps://db.cngb.org/pird.
Molecular noise of innate immunity shapes bacteria-phage ecologies
Authors: Ruess Jakob , Pleška Maroš , Guet Câlin C , Tkačik Gašper
Published: August 2018

Mathematical models have been used successfully at diverse scales of biological organization, ranging from ecology and population dynamics to stochastic reaction events occurring between individual molecules in single cells. Generally, many biological processes unfold across multiple scales, with mutations being the best studied example of how stochasticity at the molecular scale can influence outcomes at the population scale. In many other contexts, however, an analogous link between micro- and macro-scale remains elusive, primarily due to the challenges involved in setting up and analyzing multi-scale models. Here, we employ such a model to investigate how stochasticity propagates from individual biochemical reaction events in the bacterial innate immune system to the ecology of bacteria and bacterial viruses. We show analytically how the dynamics of bacterial populations are shaped by the activities of immunity-conferring enzymes in single cells and how the ecological consequences imply optimal bacterial defense strategies against viruses. Our results suggest that bacterial populations in the presence of viruses can either optimize their initial growth rate or their steady state population size, with the first strategy favoring simple and the second strategy favoring complex bacterial innate immunity.
MANIPULATION OF VOLATILE OIL PRODUCTION AND DNA PROFILE STABILITY IN EXPOSED MEDICINAL PLANTS TO SHORT-TERM DROUGHT STRESS
Authors: Abdelkader Amal , Nosair Hala
Published: August 2018

Drought stress is an environmental serious problem threatening medicinal plants. The aim of this work was monitoring the molecular aspects standing beyond the varied production of volatile oil in three medicinal plants (Ocimum basilicum, B, Mentha longifolia, M and Origanummajorana, O) after ten days of exposure to drought stress by using 250 mM mannitol as a drought inducer. The results viewed that proline has increased in all drought-stressed plants as compared to the control. Four protein bands (210, 70, 63 and 18 kDa) have been disappeared in stressed B-plant, in addition to low molecular weight-newly expressed protein bands (16-78 kDa). The varied protein polymorphism among the species ranged from 16.66% to 54.54%. RAPD-DNA technique indicated high similarity of genomic-DNA in stressed and unstressed plants. GC-MS screened intensive fluctuations within the pool of phytochemical compounds. The genomic DNA structure was generally stable under drought stress despite the expression of new proteins mediated the induction of chemical compounds with antioxidant property to cope with the drought stress.
Evidence of Müller glia conversion into retina ganglion cells using Neurogenin2
Authors: Melo Guimarães Roberta Pereira de , Landeira Bruna Soares , Coelho Diego Marques , Ferreira Golbert Daiane Cristina , Silveira Mariana S. , Linden Rafael , Melo Reis Ricardo A. de , Costa Marcos R.
Published: August 2018

Macular Degeneration, Glaucoma, and Retinitis Pigmentosa are all leading causes of irreversible visual impairment in the elderly, affecting hundreds of millions of patients. Müller glia cells (MGC), the main type of glia found in the vertebrate retina, can resume proliferation in the adult injured retina and contribute to tissue repair. Also, MGC can be genetically reprogrammed through the expression of the transcription factor (TF) Achaete-scute homolog 1 (ASCL1) into induced neurons (iNs), displaying key hallmarks of photoreceptors, bipolar and amacrine cells, which may contribute to regenerate the damaged retina. Here, we show that the TF neurogenin 2 (NEUROG2) is also sufficient to lineage-reprogram MGC into iNs. The efficiency of MGC lineage conversion by NEUROG2 is similar to that observed after expression of ASCL1. However, reprogramming efficiency is affected by previous exposure to EGF and FGF2 during the expansion of MGC population. Transduction of either Neurog2 or Ascl1 led to the upregulation of key retina neuronal genes in MGC-derived iNs, but only NEUROG2 induced a consistent increase in the expression of putative retinal ganglion cell (RGC) genes. In vivo electroporation of Neurog2 in the neonatal retina also induced a shift in the generation of retinal cell subtypes, favoring the differentiation RGCs at the expense of MGCs. Altogether, our data indicate that Neurog2 induces lineage conversion of MGCs into RGC-like iNs.
Frequency-specific brain dynamics related to prediction during language comprehension
Authors: Armeni Kristijan , Willems Roel M. , van den Bosch Antal , Schoffelen Jan-Mathijs
Published: August 2018

The brain’s remarkable capacity to process spoken language virtually in real time requires fast and efficient information processing machinery. In this study, we investigated how frequency-specific brain dynamics relate to models of probabilistic language prediction during auditory narrative comprehension. We recorded MEG activity while participants were listening to auditory stories in Dutch. Using trigram statistical language models, we estimated for every word in a story its conditional probability of occurrence. On the basis of word probabilities, we computed how unexpected the current word is given its context (word perplexity) and how (un)predictable the current linguistic context is (word entropy). We then evaluated whether source-reconstructed MEG oscillations at different frequency bands are modulated as a function of these language processing metrics. We show that theta-band source dynamics are increased in high relative to low entropy states, likely reflecting lexical computations. Beta-band dynamics are increased in situations of low word entropy and perplexity possibly reflecting maintenance of ongoing cognitive context. These findings lend support to the idea that the brain engages in the active generation and evaluation of predicted language based on the statistical properties of the input signal.
Enhanced Stability of Non-Canonical NPC2 in the symbiosome supports coral-algal symbiosis
Authors: Hambleton Elizabeth A. , Jones Victor A.S. , Maegele Ira , vaskoff David K , Sachsenheimer Timo , Guse Annika
Published: August 2018

Cnidarians such as reef-building corals depend upon nutrient transfer from intracellular symbionts, but the mechanisms and evolution of this process remain unknown. Homologues of the conserved cholesterol binder Niemann-Pick Type C2 (NPC2) in cnidarians are implicated in the transfer of sterol from symbionts. Here, we show that symbionts transfer bulk sterols to the host, host sterol utilization is plastic, and pharmacological inhibition of sterol trafficking disrupts symbiosis. Having undergone an anthozoan-specific expansion, “non-canonical” NPC2s respond to symbiosis and accumulate over time at the lysosomal-like organelle in which the symbiont resides (“symbiosome”). We demonstrate that both a non- and canonicalAiptasiaNPC2 bind symbiont-produced sterols, yet only the non-canonical homologue exhibits increased stability at low pH. We propose that symbiotic cnidarians adapted pre-existing cholesterol-trafficking machinery to function in the highly acidic symbiosome environment, allowing corals to dominate nutrient-poor shallow tropical seas worldwide.
Automated sample preparation for high-throughput single-cell proteomics
Authors: Specht Harrison , Harmange Guillaume , Perlman David H. , Emmott Edward , Niziolek Zachary , Budnik Bogdan , Slavov Nikolai
Published: August 2018

A major limitation to applying quantitative LC-MS/MS proteomics to small samples, such as single cells, are the losses incured during sample cleanup. To relieve this limitation, we developed a Minimal ProteOmic sample Preparation (mPOP) method for culture-grown mammalian cells. mPOP obviates cleanup and thus eliminates cleanup-related losses while expediting sample preparation and simplifying its automation. Bulk SILAC samples processed by mPOP or by conventional urea-based methods indicated that mPOP results in complete cell lysis and accurate relative quantification. We integrated mPOP lysis with the Single Cell ProtEomics by Mass Spectrometry (SCoPE-MS) sample preparation, and benchmarked the quantification of such samples on a Q-exactive instrument. The results demonstrate low noise and high technical reproducibility. Then, we FACS sorted single U-937, HEK-293, and mouse ES cells into 96-well plates and analyzed them by automated mPOP and SCoPE-MS. The quantified proteins enabled separating the single cells by cell-type and cell-division-cycle phase.
The Pemphigus Vulgaris antigen desmoglein-3 suppresses p53 function via the YAP-Hippo pathway
Authors: Rehman Ambreen , Cai Yang , Hünefeld Christian , Jedličková Hana , Huang Yunying , Teh M Teck , Uttagomol Jutamas , Kang Angray , Warnes Gary , Ahmad Usama , Harwood Catherine , Bergamaschi Daniele , Parkinson Eric Kenneth , Röcken Martin , Hart Ian , Wan Hong
Published: August 2018

Desmoglein-3 (Dsg3), the Pemphigus Vulgaris (PV) antigen (PVA), plays an essential role in keratinocyte cell-cell adhesion and regulates various signaling pathways implicated in the pathogenesis the PV blistering disease. We show here that expression of Dsg3 may directly influence p53, a key transcription factor governing the response to cellular stress. Dsg3 depletion caused increased p53 and apoptosis, an effect that was further enhanced by UV and mechanical strain and reversed by Dsg3 gain-of-function studies. Analysis in Dsg3-/- mouse skin confirmed increased p53/p21/caspase-3 compared to Dsg3+/- control in vivo. This Dsg3-p53 pathway involved YAP since Dsg3 forms a complex with YAP and regulates its expression and localization. Analysis of PV patient samples detected increased p53/YAP with diffuse cytoplasmic and/or nuclear staining in cells surrounding blisters. Treatment of keratinocytes with PV sera evoked pronounced p53/YAP expression. Collectively, our findings establish a novel role for Dsg3 as an anti-stress protein, via suppression of p53 function, suggesting that this pathway, involving YAP-Hippo control of skin homeostasis, is disrupted in PV.
Hemagglutinin stalk-reactive antibodies interfere with influenza virus neuraminidase activity by steric hindrance
Authors: Chen Yao-Qing , Lan Linda Yu-Ling , Huang Min , Henry Carole , Wilson Patrick C.
Published: August 2018

Hemagglutinin (HA) stalk-reactive antibodies are the basis of several current “one-shot” universal influenza vaccine efforts because they protect against a wide spectrum of influenza virus strains. The appreciated mechanism of protection by HA-stalk antibodies is to inhibit HA stalk reconfiguration, blocking viral fusion and entry. This study shows that HA stalk-reactive antibodies also inhibit neuraminidase (NA) enzymatic activity, prohibiting viral egress. NA inhibition (NI) is evident for an attached substrate but not for unattached small molecule cleavage of sialic acid. This suggests that the antibodies inhibit NA enzymatic activity through steric hindrance, thus limiting NA access to sialic acids when adjacent to HA on whole virions. Consistently, F(ab’)2 fragments that occupy reduced area without loss of avidity or disrupted HA/NA interactions show significantly reduced NI activity. Notably, HA stalk binding antibodies lacking NI activity were unable to neutralize viral infection via microneutralization assays. This work suggests that NI activity is an important component of HA-stalk antibody mediated protection.

This study reports a new mechanism of protection that is mediated by influenza hemagglutinin-stalk reactive antibodies: inhibition of neuraminidase activity by steric hindrance, blocking access of neuraminidase to sialic acids when it is abutted next to hemagglutinin on whole virions.
Cold trapped - Correcting locomotion dependent observation biases in thermal preference ofDrosophila
Authors: Giraldo Diego , Adden Andrea K. , Kuhlemann Ilyas , Gras Heribert , Geurten Bart R. H.
Published: August 2018

Sensing environmental temperatures is essential for the survival of ectothermic organisms. InDrosophila,two methodologies are used to study temperature preferences (TP) and the genes involved in thermosensation: two-choice assays and temperature gradients. Whereas two-choice assays reveal a relative TP, temperature gradients can identify the absolute Tp. One drawback of gradients is that small ectothermic animals are susceptible to cold-trapping: a physiological inability to move at the cold area of the gradient. Often cold-trapping cannot be avoided, biasing the resulting TPto lower temperatures. Two mathematical models were previously developed to correct for cold-trapping. These models, however, focus on group behaviour which can lead to overestimation of cold-trapping due to group aggregation. Here we present a mathematical model that estimates the behaviour of individualDrosophilain temperature gradients. The model takes the spatial dimension and temperature difference of the gradient into account, as well as the rearing temperature of the flies. Furthermore, it allows quantifying cold-trapping, reveals true TP, and differentiates between temperature preference and tolerance. Online simulation is hosted athttp://igloo.uni-goettingen.de. The code can be accessed athttps://github.com/zerotonin/igloo.
Evolution of DNA methylation inPapiobaboons
Authors: Vilgalys Tauras , Rogers Jeffrey , Jolly Clifford ,   Baboon Genome Analysis Consortium, Mukherjee Sayan , Tung Jenny
Published: August 2018

Changes in gene regulation have long been thought to play an important role in primate evolution. However, although a number of studies have compared genome-wide gene expression patterns across primate species, fewer have investigated the gene regulatory mechanisms that underlie such patterns, or the relative contribution of drift versus selection. Here, we profiled genome-scale DNA methylation levels from five of the six extant species of the baboon genusPapio(4–14 individuals per species). This radiation presents the opportunity to investigate DNA methylation divergence at both shallow and deeper time scales (380,000 – 1.4 million years). In contrast to studies in human populations, but similar to studies in great apes, DNA methylation profiles clearly mirror genetic and geographic structure. Divergence in DNA methylation proceeds fastest in unannotated regions of the genome and slowest in regions of the genome that are likely more constrained at the sequence level (e.g., gene exons). Both heuristic approaches and Ornstein-Uhlenbeck models suggest that DNA methylation levels at a small set of sites have been affected by positive selection, and that this class is enriched in functionally relevant contexts, including promoters, enhancers, and CpG islands. Our results thus indicate that the rate and distribution of DNA methylation changes across the genome largely mirror genetic structure. However, at some CpG sites, DNA methylation levels themselves may have been a target of positive selection, pointing to loci that could be important in connecting sequence variation to fitness-related traits.
Species-Specific Root Microbiota Dynamics in Response to Plant-Available Phosphorus
Authors: Bodenhausen Natacha , Somerville Vincent , Desirò Alessandro , Walser Jean-Claude , Borghi Lorenzo , van der Heijden Marcel G.A. , Schlaeppi Klaus
Published: August 2018

Phosphorus (P) is a limiting element for plant growth. Several root microbes, including arbuscular mycorrhizal fungi (AMF), have the capacity to improve plant nutrition and their abundance is known to depend on P fertility. However, how complex root-associated bacterial and fungal communities respond to changes in P availability remains ill-defined.

We manipulated the availability of soil P in pots and compared the root microbiota of non-mycorrhizal Arabidopsis with mycorrhizal Petunia plants. Root bacteria and fungi were profiled using ribosomal operon gene fragment sequencing, we searched for P sensitive microbes and tested whether a P sensitive core microbiome could be identified.

Root microbiota composition varied substantially by P availability. A P sensitive core microbiome was not identified as different bacterial and fungal groups responded to low-P conditions in Arabidopsis and Petunia. P sensitive microbes included Mortierellomycotina in Arabidopsis, while these were AMF and their symbiotic endobacteria in Petunia. Of note, their P-dependent root colonization was reliably quantified by sequencing.

The species-specific root microbiota dynamics suggest that Arabidopsis and Petunia evolved different microbial associations under the selection pressure of low P availability. This implies that the development of microbial products that improve P availability requires the consideration of host-species specificity.
Toll-Like Receptor-4 Disruption Suppresses Adipose Tissue Remodeling and Increases Survival During Cancer Cachexia Syndrome
Authors: Henriques Felipe , Lopes Magno A. , Franco Felipe O. , Knobl Pamela , Santos Kaltinaitis B. , Bueno Luana L. , Correa Victor A. , Bedard Alexander H. , Guilherme Adilson , Birbrair Alexander , Peres Sidney B. , Farmer Stephen R. , Batista Miguel L.
Published: August 2018

Cancer-induced cachexia, characterized by systemic inflammation, body weight loss, adipose tissue (AT) remodeling and muscle wasting, is a malignant metabolic syndrome with undefined etiology. Here, we show that Toll-like receptor 4 (TLR4) mediates AT remodeling, in particular, AT browning and inflammatory response in mice bearing Lewis lung carcinoma (LLC). LLC tumor-bearing (TB) TLR4−/− mice were spared from AT remodeling due to a reduced macrophage infiltration and adipocyte atrophy. TLR4−/− mice were also resistant to cold-induced browning of subcutaneous AT (scAT). Importantly, pharmacological inhibition of TLR4 reproduced the main protective effect against AT remodeling found in TLR4−/− TB mice. Moreover, the treatment was effective in prolonging the survival and attenuating tumor mass growth when compared to non-treated-TB animals. Further, tumor-induced elevation of circulating pro-inflammatory cytokines was similarly abolished in both genetic ablation and pharmacological inhibition of TLR4. These data suggest that TLR4 is a critical mediator and a promising therapeutic target for cancer-induced AT remodeling.

HIGHLIGHTS

Genetic ablation and pharmacological inhibition of TLR4 attenuate adipose tissue remodeling during cancer-associated cachexia;

TLR4 suppression play an essential role in the browning phenotype induced by cachexia;

Administration of TLR4 drug inhibitor increase survival and reduces tumor mass growth in tumor bearing mice;

TLR4 pathway is a promising target for cancer-cachexia therapeutic intervention.
Effects of green seaweed extract onArabidopsisearly development suggest roles for hormone signalling in plant responses to algal fertilisers
Authors: Ghaderiardakani Fatemeh , Collas Ellen , Damiano Deborah Kohn , Tagg Katherine , Graham Neil S. , Coates Juliet C.
Published: August 2018

The growing population requires sustainable, environmentally-friendly crops. The plant growth-enhancing properties of algal extracts have suggested their use as biofertilisers. The mechanism(s) by which algal extracts affect plant growth are unknown.

We examined the effects of extracts from the common green seaweedUlva intestinalison germination and root development in the model land plantArabidopsis thaliana.Ulvaextract concentrations above 0.1% inhibitedArabidopsisgermination and root growth.Ulvaextract <0.1% stimulated root growth. All concentrations ofUlvaextract inhibited lateral root formation. An abscisic-acid-insensitive mutant,abi1, showed altered sensitivity to germination- and root growth-inhibition inhibition. Ethylene- and cytokinin-insensitive mutants were partly insensitive to germination-inhibition. This suggests that different mechanisms mediate each effect ofUlvaextract on earlyArabidopsisdevelopment and that multiple hormones contribute to germination-inhibition.

Elemental analysis showed thatUlvacontains high levels of Aluminium ions (Al3+). Ethylene and cytokinin have been suggested to function in Al3+-mediated root growth inhibition: our data suggest that ifUlvaAl3+levels inhibit root growth, this is via a novel mechanism. We suggest algal extracts should be used cautiously as fertilisers, as the inhibitory effects on early development may outweigh any benefits if the concentration of extract is too high.
Stability of host-parasite systems: you must differ to coevolve
Authors: Berezovskaya Faina , Karev Georgy P. , Katsnelson Mikhail I. , Wolf Yuri I. , Koonin Eugene V.
Published: August 2018

Background

Genetic parasites are ubiquitous satellites of cellular life forms most of which host a variety of mobile genetic elements including transposons, plasmids and viruses. Theoretical considerations and computer simulations suggest that emergence of genetic parasites is intrinsic to evolving replicator systems.

Results

Using methods of bifurcation analysis, we investigated the stability of simple models of replicator-parasite coevolution in a well-mixed environment. It is shown that the simplest imaginable system of this type, one in which the parasite evolves during the replication of the host genome through a minimal mutation that renders the genome of the emerging parasite incapable of producing the replicase but able to recognize and recruit it for its own replication, is unstable. In this model, there are only either trivial or “semi-trivial”, parasite-free equilibria: an inefficient parasite is outcompeted by the host and dies off whereas an efficient one pushes the host out of existence, which leads to the collapse of the entire system. We show that stable host-parasite coevolution (a non-trivial equilibrium) is possible in a modified model where the parasite is qualitatively distinct from the host replicator in that the replication of the parasite depends solely on the availability of the host but not on the carrying capacity of the environment.

Conclusions

We analytically determine the conditions for stable host-parasite coevolution in simple mathematical models and find that a parasite that initially evolves from the host through the loss of the ability to replicate autonomously must be substantially derived for a stable host-parasite coevolution regime to be established.
BEES: Bayesian Ensemble Estimation from SAS
Authors: Bowerman Samuel , Curtis Joseph E. , Clayton Joseph , Brookes Emre H. , Wereszczynski Jeff
Published: August 2018

1

Many biomolecular complexes exist in a flexible ensemble of states in solution which are necessary to perform their biological function. Small angle scattering (SAS) measurements are a popular method for characterizing these flexible molecules due to their relative ease of use and ability to simultaneously probe the full ensemble of states. However, SAS data is typically low-dimensional and difficult to interpret without the assistance of additional structural models. In theory, experimental SAS curves can be reconstituted from a linear combination of theoretical models, although this procedure carries significant risk of overfitting the inherently low-dimensional SAS data. Previously, we developed a Bayesian-based method for fitting ensembles of model structures to experimental SAS data that rigorously avoids overfitting. However, we have found that these methods can be difficult to incorporate into typical SAS modeling workflows, especially for users that are not experts in computational modeling. To this end, we present the “Bayesian Ensemble Estimation from SAS” (BEES) program. Two forks of BEES are available, the primary one existing as module for the SASSIE webserver and a developmental version that is a standalone python program. BEES allows users to exhaustively sample ensemble models constructed from a library of theoretical states and to interactively analyze and compare each model’s performance. The fitting routine also allows for secondary data sets to be supplied, thereby simultaneously fitting models to both SAS data as well as orthogonal information. The flexible ensemble of K63-linked ubiquitin trimers is presented as an example of BEES’ capabilities.