bluuebunny/crossref_metadata_2025 huggingface dataset:
A novel mode of DnaA–DnaA interaction promotes ADP dissociation for reactivation of replication initiation activity
Authors: Sugiyama Ryo , Kasho Kazutoshi , Miyoshi Kenya , Ozaki Shogo , Kagawa Wataru , Kurumizaka Hitoshi , Katayama Tsutomu
Published: September 2019

ATP-DnaA is temporally increased to initiate replication during the cell cycle. Two chromosomal loci, DARS (DnaA-reactivating sequences) 1 and 2, promote ATP-DnaA production by nucleotide exchange of ADP-DnaA for timely initiation. ADP-DnaA complexes are constructed on DARS1 and DARS2, bearing a cluster of three DnaA-binding sequences (DnaA boxes I−III), promoting ADP dissociation. Although DnaA has an AAA+ domain, which ordinarily directs construction of oligomers in a head-to-tail manner, DnaA boxes I and II are oriented oppositely. In this study, we constructed a structural model of a head-to-head dimer of DnaA AAA+ domains, and analyzed residues residing on the interface of the model dimer. Gln208 was specifically required for DARS-dependent ADP dissociation in vitro, and in vivo analysis yielded consistent results. Additionally, ADP release from DnaA protomers bound to DnaA boxes I and II was dependent on Gln208 of the DnaA protomers, and DnaA box III-bound DnaA did not release ADP nor require Gln208 for ADP dissociation by DARS–DnaA complexes. Based on these and other findings, we propose a model for DARS–DnaA complex dynamics during ADP dissociation, and provide novel insight into the regulatory mechanisms of DnaA and the interaction modes of AAA+ domains.
Human cytomegalovirus seropositivity is associated with decreased survival in glioblastoma patients
Authors: Foster Haidn , Piper Keenan , DePledge Lisa , Li Hsin-Fang , Scanlan James , Jae-Guen Yoon , Boeckh Michael , Cobbs Charles
Published: September 2019

Background

Human cytomegalovirus (HCMV) is an oncomodulatory human herpesvirus that has been detected in glioblastoma (GBM) and is associated with worse prognosis in patients with the disease. The effects of HCMV systemic infection on survival in GBM patients, however, are largely unknown. We aimed to determine the association between HCMV serostatus at diagnosis and survival via a retrospective cohort study of GBM patients.

Methods

Plasma from 188 GBM patients treated at the Ben and Catherine Ivy Center (Seattle, WA) was tested for HCMV serostatus via enzyme-linked immunosorbent assays of anti-HCMV immunoglobulin (Ig)G. HCMV IgG serostatus was analyzed with respect to each patient’s progression-free and overall survival (OS) via log-rank and multivariable Cox regression analysis.

Results

Ninety-seven of 188 (52%) patients were anti-HCMV IgG seropositive. Median OS was decreased in the IgG+ cohort (404 days) compared to IgG− patients (530 days; P = .0271). Among O6-methylguanine-DNA methyltransferase (MGMT) unmethylated patients (n = 96), median OS was significantly decreased in IgG+ patients (336 days) compared to IgG− patients (510 days; P = .0094). MGMT methylation was associated with improved OS in IgG+ patients versus those who were unmethylated (680 vs 336 days; P = .0096), whereas no such association was observed among IgG− patients.

Conclusions

In this study, HCMV seropositivity was significantly associated with poorer OS in GBM patients. This finding suggests prior infection with HCMV may play an important role in GBM patient outcomes, and anti-HCMV antibodies may, therefore, prove a valuable prognostic tool in the management of GBM patients.
The Effectiveness of Radiofrequency Ablation of Medial Branch Nerves for Chronic Lumbar Facet Joint Syndrome in Patients Selected by Guideline-Concordant Dual Comparative Medial Branch Blocks
Authors: Conger Aaron , Burnham Taylor , Salazar Fabio , Tate Quinn , Golish Mathew , Petersen Russell , Cunningham Shellie , Teramoto Masaru , Kendall Richard , McCormick Zachary L
Published: September 2019

Objectives

Although the effectiveness of lumbar medial branch radiofrequency ablation (RFA) for the treatment of zygapophyseal joint (z-joint)–mediated low back pain has been characterized, few studies have described outcomes in patients selected using a guideline-concordant paradigm of ≥80% pain relief with dual comparative medial branch blocks (MBBs). We investigated long-term treatment outcomes of patients selected according to this paradigm.

Design

Cross-sectional cohort study.

Methods

The medical records of 111 consecutive patients were reviewed; 85 met inclusion criteria. A standardized telephone survey was used to capture current numerical rating scale (NRS) and Patient Global Impression of Change (PGIC) scores. The primary outcome was the proportion of patients reporting ≥50% reduction of index pain. Binary logistic regression analysis was performed to explore associations between the primary outcome and covariates, including age, duration of pain, presence of scoliosis, degenerative spondylolisthesis, and >75% disc height loss.

Results

At six to 12, 12–24, and >24 months, 63.2% (95% confidence interval [CI] = 41–85%), 65.6% (95% CI = 49–82%), and 44.1% (95% CI = 27–61%) of patients reported a ≥50% pain reduction (P = 0.170), respectively. At a minimum of six months, 70.6% of patients reported a pain reduction of two or more points (minimally clinically important change), and 54.1% reported a PGIC score consistent with “much improved” or better. Older age and a smaller Cobb angle were associated with a ≥50% pain reduction (P < 0.05).

Conclusion

Lumbar medial branch RFA is an effective, durable treatment for a significant proportion of patients with recalcitrant lumbar z-joint pain when candidacy is determined by the guideline-concordant paradigm of ≥80% pain relief with dual comparative MBBs.
Gravity in the Exchange Rate Factor Structure
Authors: Lustig Hanno , Richmond Robert J
Published: September 2019

We relate the risk characteristics of currencies to measures of physical, cultural, and institutional distance. Currencies of countries which are more distant from other countries are more exposed to systematic currency risk. This is due to a gravity effect in the factor structure of exchange rates: When a currency appreciates against a basket of other currencies, its bilateral exchange rate appreciates more against currencies of distant countries. As a result, currencies of peripheral countries are more exposed to systematic variation than currencies of central countries. Trade network centrality best predicts a currency’s average exposure to systematic risk.
MRI of the sacroiliac joints in athletes: recognition of non-specific bone marrow oedema by semi-axial added to standard semi-coronal scans
Authors: Weber Ulrich , Jurik Anne Grethe , Zejden Anna , Larsen Ejnar , Jørgensen Steen Hylgaard , Rufibach Kaspar , Schioldan Christian , Schmidt-Olsen Søren
Published: September 2019

Objective

Assessment of combined semi-axial and semi-coronal SI joint MRI in two cohorts of young athletes to explore frequency and topography of non-specific bone marrow oedema (BMO), its association with four constitutional SI joint features, and potential restriction of false-positive assignments of Assessment of SpondyloArthritis International Society-defined sacroiliitis on standard semi-coronal scans alone.

Methods

Combined semi-axial and semi-coronal SI joint MRI scans of 20 recreational runners before/after running and 22 elite ice-hockey players were evaluated by three blinded readers for BMO and its association with four constitutional SI joint features: vascular partial volume effect, deep iliac ligament insertion, fluid-filled bone cyst and lumbosacral transitional anomaly. Scans of TNF-treated spondyloarthritis patients served to mask readers. We analysed distribution and topography of BMO and SI joint features across eight anatomical SI joint regions (upper/lower ilium/sacrum, subdivided in anterior/posterior slices) descriptively, as concordantly recorded by ⩾2/3 readers on both MRI planes. BMO confirmed on both scans was compared with previous evaluation of semi-coronal MRI alone, which met the Assessment of SpondyloArthritis International Society definition for active sacroiliitis.

Results

Perpendicular semi-axial and semi-coronal MRI scans confirmed BMO in the SI joint of every fourth young athlete, preferentially in the anterior upper sacrum. BMO associated with four constitutional SI joint features was observed in 20–36% of athletes, clustering in the posterior lower ilium. The proportion of Assessment of SpondyloArthritis International Society-positive sacroiliitis recorded on the semi-coronal plane alone decreased by 33–56% upon amending semi-axial scans.

Conclusion

Semi-axial combined with standard semi-coronal scans in MRI protocols for sacroiliitis facilitated recognition of non-specific BMO, which clustered in posterior lower ilium/anterior upper sacrum.
OCCUPATIONAL RADIATION DOSE PERFORMING HEPATOBILIARY MINIMALLY INVASIVE PROCEDURES IN CHILDREN WEIGHING LESS THAN 20 kg
Authors: Gerasia Roberta , Cannataci Christine , Maruzzelli Luigi , Caruso Calogero , Liotta Ferdinanda , Cucchiara Antonino , Cortis Kelvin , Miraglia Roberto
Published: September 2019

Our objective is to retrospectively evaluate the effective dose (E) of operators performing pediatric Hepatobiliary Minimally Invasive Procedures (HMIP). Between October 2015 and December 2017, 58 consecutive HMIP were performed on 26 children weighing less than 20 kg (mean 12.3 kg, median 13 kg, range 2.4–20 kg). About 31 vascular procedures (n = 9 hepatic venograms with/without stenting; n = 9 retrograde wedge portography; n = 8 transhepatic portography with angioplasty and/or stenting and n = 5 hepatic arteriography/embolization) and 27 non-vascular procedures (n = 6 percutaneous transhepatic biliary drainage (PTBD); n = 3 bilioplasty; n = 15 biliary catheter change and n = 3 cholangiogram) were performed. Electronic personal dosimeters were used to measure radiation doses to the interventional radiologist, radiographer and anesthesia nurse. The results shows the highest mean effective dose: interventional radiologist’s in PTBD (1.18 μSv); radiographer’s in hepatic veins phlebography with/without stenting (0.25 μSv) and nurse’s in hepatic arteriography/embolization (0.26 μSv). Operators’ E can vary depending on the complexity of procedure performed and the position of the operators within the angiosuite.
Contentions over World Culture: The Rise of Legal Restrictions on Foreign Funding to NGOs, 1994–2015
Authors: Bromley Patricia , Schofer Evan , Longhofer Wesley
Published: September 2019

The last two decades have witnessed an unprecedented rise in government restrictions on foreign funding to nongovernmental organizations (NGOs). Often in the name of defending the nation from outside influences, over 60 countries have implemented laws limiting foreign funding to NGOs. We use event history analyses to evaluate domestic and global explanations for the adoption of these policies over the period 1994–2015. Prior work has argued that funding restrictions result from real or perceived threats to political regimes, especially in countries with competitive elections. We add to this story by situating it in a larger global and cultural context: new funding laws are part of a growing backlash against the liberal international order, which has long sponsored international and domestic NGOs devoted to issues such as human rights and the environment. In an era of increasing resistance toward globally linked civil society groups—the primary carriers of liberal world society—NGO funding restrictions are now diffusing widely across the international system. We argue that restriction policies will be most common among countries that are linked to illiberal or anti-Western organizations and discourses in the international community. Moreover, adoption will accelerate as more countries do it, representing a growing “wave” or backlash against the liberal international order. Findings support the prior literature as well as our new arguments regarding illiberal international organizations and global backlash.
Inferring putative transmission clusters with Phydelity
Authors: Han Alvin X , Parker Edyth , Maurer-Stroh Sebastian , Russell Colin A
Published: September 2019

Current phylogenetic clustering approaches for identifying pathogen transmission clusters are limited by their dependency on arbitrarily defined genetic distance thresholds for within-cluster divergence. Incomplete knowledge of a pathogen’s underlying dynamics often reduces the choice of distance threshold to an exploratory, ad hoc exercise that is difficult to standardise across studies. Phydelity is a new tool for the identification of transmission clusters in pathogen phylogenies. It identifies groups of sequences that are more closely related than the ensemble distribution of the phylogeny under a statistically principled and phylogeny-informed framework, without the introduction of arbitrary distance thresholds. Relative to other distance threshold- and model-based methods, Phydelity outputs clusters with higher purity and lower probability of misclassification in simulated phylogenies. Applying Phydelity to empirical datasets of hepatitis B and C virus infections showed that Phydelity identified clusters with better correspondence to individuals that are more likely to be linked by transmission events relative to other widely used non-parametric phylogenetic clustering methods without the need for parameter calibration. Phydelity is generalisable to any pathogen and can be used to identify putative direct transmission events. Phydelity is freely available at https://github.com/alvinxhan/Phydelity.
Diapause is not selected as a bet-hedging strategy in insects: a meta-analysis of reaction norm shapes
Authors: Joschinski Jens , Bonte Dries
Published: September 2019

Many organisms escape from lethal climatological conditions by entering a resistant resting stage called diapause, which needs to be optimally timed with seasonal change. As climate change exerts selection pressure on phenology, the evolution of mean diapause timing, but also of phenotypic plasticity and bet-hedging strategies is expected. Especially the latter as a strategy to cope with unpredictability is little considered in the context of climate change.

Contemporary patterns of phenological strategies across a geographic range may provide information about their evolvability. We thus extracted 458 diapause reaction norms from 60 studies. First, we correlated mean diapause timing with mean winter onset. Then we partitioned the reaction norm variance into a temporal component (phenotypic plasticity) and among-offspring variance (diversified bet-hedging) and correlated this variance composition with predictability of winter onset. Mean diapause timing correlated reasonably well with mean winter onset, except for populations at high latitudes, which apparently failed to track early onsets. Variance among offspring was, however, limited and correlated only weakly with environmental predictability, indicating little scope for bet-hedging. The apparent lack of phenological bet-hedging strategies may pose a risk in a less predictable climate, but we also highlight the need for more data on alternative strategies.
Single-cell RNA-sequencing reveals profibrotic roles of distinct epithelial and mesenchymal lineages in pulmonary fibrosis
Authors: Habermann Arun C. , Gutierrez Austin J. , Bui Linh T. , Yahn Stephanie L. , Winters Nichelle I. , Calvi Carla L. , Peter Lance , Chung Mei-I , Taylor Chase J. , Jetter Christopher , Raju Latha , Roberson Jamie , Ding Guixiao , Wood Lori , Sucre Jennifer MS , Richmond Bradley W. , Serezani Ana P. , McDonnell Wyatt J. , Mallal Simon B. , Bacchetta Matthew J. , Loyd James E. , Shaver Ciara M. , Ware Lorraine B. , Bremner Ross , Walia Rajat , Blackwell Timothy S. , Banovich Nicholas E. , Kropski Jonathan A.
Published: September 2019

Pulmonary fibrosis is a form of chronic lung disease characterized by pathologic epithelial remodeling and accumulation of extracellular matrix. In order to comprehensively define the cell types, mechanisms and mediators driving fibrotic remodeling in lungs with pulmonary fibrosis, we performed single-cell RNA-sequencing of single-cell suspensions from 10 non-fibrotic control and 20 PF lungs. Analysis of 114,396 cells identified 31 distinct cell types. We report a remarkable shift in epithelial cell phenotypes occurs in the peripheral lung in PF, and identify several previously unrecognized epithelial cell phenotypes including a KRT5−/KRT17+, pathologic ECM-producing epithelial cell population that was highly enriched in PF lungs. Multiple fibroblast subtypes were observed to contribute to ECM expansion in a spatially-discrete manner. Together these data provide high-resolution insights into the complexity and plasticity of the distal lung epithelium in human disease, and indicate a diversity of epithelial and mesenchymal cells contribute to pathologic lung fibrosis.

One Sentence Summary

Single-cell RNA-sequencing provides new insights into pathologic epithelial and mesenchymal remodeling in the human lung.
Genetic Interaction between RLM1 and F-box Motif Encoding gene SAF1 Contributes to Stress Response inSaccharomyces cerevisiae
Authors: Sharma Meenu , Verma V. , Bairwa Narendra K
Published: September 2019

Stress response is mediated by transcription of stress responsive genes. F-box motif protein Saf1 involves in SCF-E3 ligase mediated degradation of the adenine deaminase, Aah1 upon nutrient stress. Four transcription regulators, BUR6, MED6, SPT10, SUA7, have been reported for SAF1 gene in genome database ofSaccharomyces cerevisiae.Here in this study anin-silcoanalysis of gene expression and transcription factor databases was carried out to understand the regulation of SAF1 gene expression during stress for hypothesis generation and experimental analysis. The GEO profile database analysis showed increased expression of SAF1 gene when treated with clioquinol, pterostilbene, gentamicin, hypoxia, genotoxic, desiccation, and heat stress, in WT cells. SAF1 gene expression in stress conditions correlated positively whereas AAH1 expression negatively with RLM1 transcription factor, which was not reported earlier. Based on analysis of expression profile and regulatory association of SAF1 and RLM1, we hypothesized that inactivation of both the genes may contribute to stress tolerance. The experimental analysis with the double mutant,saf1Δrlm1Δfor cellular growth response to stress causing agents, showed tolerance to calcofluor white, SDS, and hydrogen peroxide. On the contrary,saf1Δrlm1Δshowed sensitivity to MMS, HU, DMSO, Nocodazole, Benomyl stress. Based on in-silicoand experimental data we suggest that SAF1 and RLM1 both interact genetically in differential response to genotoxic and general stressors.
Learning improves decoding of odor identity with phase-referenced oscillations in the olfactory bulb
Authors: Losacco Justin , Ramirez-Gordillo Daniel , Gilmer Jesse , Restrepo Diego
Published: September 2019

Local field potential oscillations reflect temporally coordinated neuronal ensembles— coupling distant brain regions, gating processing windows, and providing a reference for spike timing-based codes. In phase amplitude coupling (PAC), the amplitude of the envelope of a faster oscillation is larger within a phase window of a slower carrier wave. Here, we characterized PAC, and the related theta phase-referenced high gamma and beta power (PRP), in the olfactory bulb of mice learning to discriminate odorants. PAC changes throughout learning, and odorant-elicited changes in PRP increase for rewarded and decrease for unrewarded odorants. Contextual odorant identity (is the odorant rewarded?) can be decoded from peak PRP in animals proficient in odorant discrimination, but not in naïve mice. As the animal learns to discriminate the odorants the dimensionality of PRP decreases. Therefore, modulation of phase-referenced chunking of information in the course of learning plays a role in early sensory processing in olfaction.

Significance

Early processing of olfactory information takes place in circuits undergoing slow frequency theta oscillations generated by the interplay of olfactory input modulated by sniffing and centrifugal feedback from downstream brain areas. Studies in the hippocampus and cortex suggest that different information “chunks” are conveyed at different phases of the theta oscillation. Here we show that in the olfactory bulb, the first processing station in the olfactory system, the amplitude of high frequency gamma oscillations encodes for information on whether an odorant is rewarded when it is observed at the peak phase of the theta oscillation. Furthermore, encoding of information by the theta phase-referenced gamma oscillations becomes more accurate as the animal learns to differentiate two odorants.
immuneSIM: tunable multi-feature simulation of B- and T-cell receptor repertoires for immunoinformatics benchmarking
Authors: Weber Cédric R. , Akbar Rahmad , Yermanos Alexander , Pavlović Milena , Snapkov Igor , Sandve Geir Kjetil , Reddy Sai T. , Greiff Victor
Published: September 2019

B- and T-cell receptor repertoires of the adaptive immune system have become a key target for diagnostics and therapeutics research. Consequently, there is a rapidly growing number of bioinformatics tools for immune repertoire analysis. Benchmarking of such tools is crucial for ensuring reproducible and generalizable computational analyses. Currently, however, it remains challenging to create standardized ground truth immune receptor repertoires for immunoinformatics tool benchmarking. Therefore, we developed immuneSIM, an R package that allows the simulation of native-like and aberrant synthetic full length variable region immune receptor sequences. ImmuneSIM enables the tuning of the immune receptor features: (i) species and chain type (BCR, TCR, single, paired), (ii) germline gene usage, (iii) occurrence of insertions and deletions, (iv) clonal abundance, (v) somatic hypermutation, and (vi) sequence motifs. Each simulated sequence is annotated by the complete set of simulation events that contributed to its in silico generation. immuneSIM permits the benchmarking of key computational tools for immune receptor analysis such as germline gene annotation, diversity and overlap estimation, sequence similarity, network architecture, clustering analysis, and machine learning methods for motif detection.

Availability

The package is available viahttps://github.com/GreiffLab/immuneSIMand will also be available at CRAN (submitted). The documentation is hosted athttps://immuneSIM.readthedocs.io.

Contact

victor.greiff@medisin.uio.no,sai.reddy@ethz.ch
Cytokinin promotes jasmonic acid accumulation in the control of maize leaf growth
Authors: Uyehara Aimee N. , Del Valle-Echevarria Angel R. , Hunter Charles T. , Nelissen Hilde , Demuynck Kirin , Cahill James F. , Jander Georg , Muszynski Michael G.
Published: September 2019

Growth of plant organs results from the combined activity of cell division and cell expansion. The coordination of these two processes depends on the interplay between multiple hormones that determine final organ size. Using the semidominant Hairy Sheath Frayed1 (Hsf1) maize mutant, that hypersignals the perception of cytokinin (CK), we show that CK can reduce leaf size and growth rate by decreasing cell division. Linked to CK hypersignaling, the Hsf1 mutant has increased jasmonic acid (JA) content, a hormone that can inhibit cell division. Treatment of wild type seedlings with exogenous JA reduces maize leaf size and growth rate, while JA deficient maize mutants have increased leaf size and growth rate. Expression analysis revealed increased transcript accumulation of several JA pathway genes in the Hsf1 leaf growth zone. A transient treatment of growing wild type maize shoots with exogenous CK also induced JA pathway gene expression, although this effect was blocked by co-treatment with cycloheximide. Together our results suggest that CK can promote JA accumulation possibly through increased expression of specific JA pathway genes.

One sentence summary

Cytokinin-signaling upregulates the jasmonate biosynthesis pathway, resulting in jasmonate accumulation and influences on maize leaf growth.
β-HPV 8E6 Dysregulates the Hippo Signaling Pathway and Induces Aneuploidy
Authors: Dacus Dalton , McCallister Tristan X. , Cotton Celeste , Riforgiate Elizabeth , Wallace Nicholas A.
Published: September 2019

Beta genus human papillomaviruses (β-HPVs) are associated with cutaneous squamous cell carcinomas (cSCCs) in a subset of immunocompromised patients. Although β-HPVs are not necessary for tumor maintenance, they are hypothesized to destabilize the genome in the early stages of cancer development. Supporting this idea, β-HPV’s 8E6 protein attenuates p53 accumulation after failed cytokinesis. This paper identifies the mechanism of this abatement. We show β-HPV 8E6 dysregulates the Hippo signaling pathway (HP). It increases pro-proliferative gene expression, enhances TEAD activity and promotes cell growth. β-HPV 8E6 also reduces LATS activation and p53-mediated apoptosis following unsuccessful division of mitotic cells. These phenotypes are dependent on β-HPV 8E6 binding and destabilizing a cellular histone acetyltransferase, p300. Despite circumventing apoptosis, β-HPV 8E6 caused increased senescence after unsuccessful cytokinesis. We linked this lack of growth to the viral protein’s inability to prevent cytoplasmic sequestration of the HP transcription factor, YAP. We also show that increased telomerase reverse transcriptase activity (a common alteration in cSCCs) acts synergistically with β-HPV 8E6 to promote cellular proliferation after abortive cytokinesis. While β-HPV 8E6 promoted aneuploidy on its own, this genome destabilization is amplified in cells that do not divide after mitosis. Although our group and others have previously described inhibition of DNA repair, to the best of our knowledge this marks the first time that a β-HPV protein has been connected to chromosome level changes in the cellular genome. This represents a substantial escalation in the known genome destabilizing properties likely to occur during a β-HPV infection.

IMPORTANCE

There is mounting evidence that β-HPVs contribute to cSCCs development in immunocompromised populations. They may also augment UV’s mutagenic potential, increasing cancer risk in the general population. We demonstrate that β-HPV 8E6 dysregulates the Hippo signaling pathway (HP). HP regulates cell growth and apoptosis in response to a myriad of stimuli, including failed cytokinesis. β-HPV 8E6 attenuates phosphorylation of the HP kinase, LATS, decreasing some but not all downstream signaling events. This allows binucleated cells to avoid apoptosis, however they succumb to senescence. We show that β-HPV 8E6 synergizes with a common cSCC mutation (telomerase activation) to avoid both apoptosis and senescence. We did not find any telomerase immortalized β-HPV 8E6 expressing cells that were not aneuploid after aberrant cytokinesis. This represents a substantial escalation in β-HPV E6’s known mutagenic potential.
Dental emergency: scoping review
Authors: Frichembruder Karla , dos Santos Camila Mello , Hugo Fernando Neves
Published: September 2019

Part of the oral health care in the care network encompasses users in cases of emergency. This study proposed to map the determinants of the use of dental care services within the health care network to address dental emergencies of the Brazilian Unified Health System (UHS) and to verify the main gaps in the research in this area. This is a scoping review that took place in 2018 using Andersen’s behavioral model as a reference. A total of 16 studies, out of 3786 original articles identified, were included and reviewed. Two reviewers independently conducted the selection process and the decision was consensually taken. The mapping of the determinants revealed a greater number of enabling factors and a larger gap in results. Greater use of the emergency service was registered by people in pain, women, adults, from an urban area, with a lower income, and less education. In future studies, primary surveys are recommended, which include all ages, analyzing different groups of needs and users that take into account the country’s northern region and the different subjects pointed out in this review.
Can scientists fill the science journalism void? Online public engagement with science stories authored by scientists
Authors: David Yael Barel-Ben , Garty Erez S. , Baram-Tsabari Ayelet
Published: September 2019

In many countries the public’s main source of information about science and technology is the mass media. Unfortunately, in recent years traditional journalism has experienced a collapse, and science journalism has been a major casualty. One potential remedy is to encourage scientists to write for news media about science. On these general news platforms, scientists’ stories would have to compete for attention with other news stories on hard (e.g. politics) and entertaining (e.g. celebrity news) topics written by professional writers. Do they stand a chance?

This study aimed to quantitatively characterize audience interactions as an indicator of interest in science news stories authored by early career scientists (henceforth ‘scientists’) trained to function as science reporters, as compared to news items written by reporters and published in the same news outlets.

To measure users’ behavior, we collected data on the number of clicks, likes, comments and average time spent on page. The sample was composed of 150 science items written by 50 scientists trained to contribute popular science stories in the Davidson Institute of Science Education reporters’ program and published on two major Israeli news websites -MakoandYnetbetween July 2015 to January 2018. Each science item was paired with another item written by the website’s organic reporter, and published on the same channel as the science story (e.g., tourism, health) and the same close time. Overall significant differences were not found in the public’s engagement with the different items. Although, on one website there was a significant difference on two out of four engagement types, the second website did not have any difference, e.g., people did not click, like or comment more on items written by organic reporters than on the stories written by scientists. This creates an optimistic starting point for filling the science news void by scientists as science reporters.
Effects of Inaccurate Response Function Calibration on Characteristics of the Fiber Orientation Distribution in Diffusion MRI
Authors: Guo Fenghua , Tax Chantal M.W. , Luca Alberto De , Viergever Max A. , Heemskerk Anneriet , Leemans Alexander
Published: September 2019

Diffusion MRI of the brain enables to quantify white matter fiber orientations noninvasively. Several approaches have been proposed to estimate such characteristics from diffusion MRI data with spherical deconvolution being one of the most widely used methods. Constrained spherical deconvolution requires to define – or derive from the data – a response function, which is used to compute the fiber orientation distribution (FOD). This definition or derivation is not unequivocal and can thus result in different characteristics of the response function which are expected to affect the FOD computation and the subsequent fiber tracking. In this work, we explored the effects of inaccuracies in the shape and scaling factors of the response function on the FOD characteristics. With simulations, we show that underestimation of the shape factor in the response functions has a larger effect on the FOD peaks than overestimation of the shape factor, whereas the latter will cause more spurious peaks. Moreover, crossing fiber populations with a smaller separation angle were more sensitive to the response function inaccuracy than fiber populations with more orthogonal separation angles. Furthermore, the FOD characteristics show deviations as a result of modified shape and scaling factors of the response function. Results with the in vivo data demonstrate that the deviations of the FODs and spurious peaks can further deviate the termination of propagation in fiber tracking. This work highlights the importance of proper definition of the response function and how specific calibration factors can affect the FOD and fiber tractography results.
Vegetation and soil seedbank dynamics inParthenium hysterophorusL. invaded subtropical grassland in Nepal
Authors: Rokaya Maan Bahadur , Khatri-Chettri Jyoti , Ghimire Shiba Raj , Shrestha Bharat Babu
Published: September 2019

Parthenium hysterophorusis a noxious invasive weed and is ever expanding in its introduced range including Nepal. Understanding vegetation dynamics including soil seedbank inPartheniuminvaded communities and the growth pattern of the weed itself is essential for effective management ofParthenium. We monitored growth ofParthenium(height, density, cover and soil seedbank) and plant species composition of associated species for 5-year period from 2009 in a grassland invaded byPartheniumin south-central Nepal. We found thatPartheniumcover and height decreased from 2009 to 2010 and then slightly increased in 2013.Partheniumdensity decreased from 2009 to 2010 and then was variable until 2013. Year × grazing interactions had significant effect onPartheniumcover and density.Partheniumsoil seedbank was eight times higher near the soil surface than in deep soil. It increased from 2009 to 2012 but decreased in 2013. Seedbank was also affected by interactions of year × depth, depth × grazing, and year × depth × grazing. Altogether, 87 plant species were recorded inPartheniuminvaded sites and their species richness decreased until 2012 but slightly increased in 2013. The composition of associated plant species was affected by animal grazing intensity,Partheniumdensity, cover, and their interactions.Partheniuminvasion has been ever increasing in our study site and many palatable plant species are under potential threat. Thus, there is an urgent need to carry out awareness campaign, formulate proper management plans, and implement such plans properly to managePartheniumweed in Nepal.
Immediate early gene kakusei plays a role in the daily foraging and learning of honey bees
Authors: Singh Asem Surindro , Cappelletti Pamela , Feligioni Marco
Published: September 2019

kakuseiis a non-coding RNA that is overexpressed in foraging bee brain. This study describes a fundamental role of the IEGkakuseiduring the daily foraging of honey bees.kakuseiwas found to be transiently upregulated within two hours during rewarded foraging. Interestingly, during unrewarded foraging the gene was also found to be up-regulated, but immediately lowered as food was not rewarded. Moreover, thekakuseioverexpression was diminished within a very short time when the time schedule of feeding was changed. This indicates the potential role ofkakuseion the motivation of learned reward foraging, reflecting associative learning memory. These results provide evidence for a dynamic role ofkakuseiduring foraging of bees, and eventually its possible involvement in learning and memory. Thus thekakuseigene could be used as key search tool in finding distinct molecular pathways that mediate diverse behavioral components of foraging.
Specialization for cell-free or cell-to-cell spread of BAC-cloned HCMV strains is determined by factors beyond the UL128-131 and RL13 loci
Authors: Schultz Eric P. , Lanchy Jean-Marc , Day Le Zhang , Yu Qin , Peterson Christopher , Preece Jessica , Ryckman Brent J.
Published: September 2019

It is widely held that clinical isolates of human cytomegalovirus (HCMV) are highly cell-associated, and mutations affecting the UL128-131 and RL13 loci that arise in culture lead to the appearance of a cell-free spread phenotype. The BAC-clone Merlin (ME), expresses abundant UL128-131, is RL13-impaired and produces low infectivity virions in fibroblasts, whereas TB40/e (TB) and TR are low in UL128-131, RL13-intact and produce virions of much higher infectivity. Despite these differences, quantification of spread by flow cytometry revealed remarkably similar spread efficiencies in fibroblasts. In epithelial cells, ME spread more efficiently, consistent with robust UL128-131 expression. Strikingly, ME spread far better than TB or TR in the presence of neutralizing antibodies on both cell types, indicating that ME is not simply deficient at cell-free spread, but is particularly efficient at cell-to-cell spread, whereas TB and TR cell-to-cell spread is poor. Sonically disrupted ME-infected cells contained scant infectivity, suggesting that the efficient cell-to-cell spread mechanism of ME depends on features of the intact cells such as junctions or intracellular trafficking processes. Even when UL128-131 was transcriptional repressed, cell-to-cell spread of ME was still more efficient than TB or TR. Moreover, RL13 expression comparably reduced both cell-free and cell-to-cell spread of all three strains, suggesting that it acts at a stage of assembly and/or egress common to both routes of spread. Thus, HCMV strains can be highly specialized for either for cell-free or cell-to-cell spread and these phenotypes are determined by factors beyond the UL128-131 or RL13 loci.

IMPORTANCE

Both cell-free and cell-to-cell spread are likely important for the natural biology of HCMV. In culture, strains clearly differ in their capacity for cell-free spread as a result of differences in the quantity and infectivity of extracellular released progeny. However, it has been unclear whether “cell-associated” phenotypes are simply the result of poor cell-free spread, or are indicative of particularly efficient cell-to-cell spread mechanisms. By measuring the kinetics of spread at early time points, we were able to show that HCMV strains can be highly specialized to either cell-free or cell-to-cell mechanisms, and this was not strictly linked the efficiency of cell-free spread. Our results provide a conceptual approach to evaluating intervention strategies for their ability to limit cell-free or cell-to-cell spread as independent processes.
Modelling the epidemiology of residual Plasmodium vivax malaria in a heterogeneous host population: a case study in the Amazon Basin
Authors: Corder Rodrigo M. , Ferreira Marcelo U. , Gomes M. Gabriela M.
Published: September 2019

The overall malaria burden in the Americas has decreased dramatically over the past two decades, but residual transmission pockets persist across the Amazon Basin, where Plasmodium vivax is the predominant infecting species. Current elimination efforts require a better quantitative understanding of malaria transmission dynamics for planning, monitoring, and evaluating interventions at the community level. This can be achieved with mathematical models that properly account for risk heterogeneity in communities approaching elimination, where few individuals disproportionately contribute to overall malaria prevalence, morbidity, and onwards transmission. Here we analyse demographic information combined with routinely collected malaria morbidity data from the town of Mâncio Lima, the main urban transmission hotspot of Brazil. We estimate the proportion of high-risk subjects in the host population by fitting compartmental susceptible-infected-susceptible (SIS) transmission models simultaneously to age-stratified vivax malaria incidence densities and the frequency distribution of P. vivax malaria attacks experienced by each individual over 12 months. Simulations with the best-fitting SIS model indicate that 20% of the hosts contribute 86% of the overall vivax malaria burden. Despite the low overall force of infection typically found in the Amazon, about one order of magnitude lower than that in rural Africa, high-risk individuals gradually develop clinical immunity following repeated infections and eventually constitute a substantial infectious reservoir comprised of asymptomatic parasite carriers that is overlooked by routine surveillance but likely fuels onwards malaria transmission. High-risk individuals therefore represent a priority target for more intensive and effective interventions that may not be readily delivered to the entire community.
A role of the Nse4 kleisin and Nse1/Nse3 KITE subunits in the ATPase cycle of SMC5/6
Authors: Vondrova L. , Adamus M. , Nociar M. , Kolesar P. , Oliver A.W. , Palecek J.J.
Published: September 2019

The SMC (Structural Maintenance of Chromosomes) complexes are composed of SMC dimers, kleisin and kleisin-interacting subunits. Mutual interactions of these subunits constitute the basal architecture of the SMC complexes. Particularly, terminal domains of the kleisin subunit bridge the SMC head domains of the SMC molecules. Binding of ATP molecules to the heads and their hydrolysis alter the shape of long SMC molecules (from rod-like to open-ring shapes) and power them with motor activity. The kleisin-interacting (HAWK or KITE) subunits bind kleisin linker regions and regulate such dynamic activities.

We developed new systems to follow the interactions between SMC5/6 subunits and stability of the SMC5/6 complexes. First, we show that the N-terminal domain of the Nse4 kleisin molecule binds to the SMC6 neck and bridges it to the SMC5 head. Second, binding of the Nse1 and Nse3 KITE proteins to the Nse4 linker part increases stability of the ATP-free SMC5/6 complex. In contrast, binding of ATP to the SMC5/6 complex containing KITE subunits significantly decreases its stability. Elongation of the Nse4 linker partially suppresses instability of the ATP-bound complex, suggesting that the binding of the KITE proteins to the Nse4 linker constrains its limited size. Our data suggest that the KITE proteins may shape the Nse4 linker to fit the ATP-free complex optimally and to facilitate opening of the complex upon ATP binding. This mechanism suggests an important role of the KITE subunits in the dynamics of the SMC5/6 complexes.

AUTHOR SUMMARY

The SMC5/6 complex is member of the Structural maintenance of chromosomes (SMC) family, key organizers of both prokaryotic and eukaryotic genomes. Their architecture and dynamics (driven by ATP binding and hydrolysis) are essential for cellular processes, like chromatin segregation, condensation, replication and repair. In this paper, we described conserved mode of the Nse4 kleisin subunit binding to the SMC6 (similar to cohesin and condensin) and its bridging role. Furthermore, we showed different impact of the binding of the Nse1-Nse3 KITE subunits to the Nse4 kleisin bridge. Our study suggested that the KITE proteins modulate the stability of the SMC5/6 complex, depending on its binding and hydrolysis of ATP. Our findings uncover molecular mechanisms underlying dynamics of the SMC5/6 complexes.
Thickening of the cell wall increases the resistance ofS. cerevisiaeto commercial formulations of glyphosate
Authors: Ravishankar Apoorva , Pupo Amaury , Gallagher Jennifer E.G.
Published: September 2019

The use of glyphosate-based herbicides is widespread and despite its extensive use, its effects are yet to be deciphered completely. The additives in commercial formulations of glyphosate, though labeled as inert when used individually, have adverse effects when used in combination with other additives and the active ingredient. As a species,Saccharomyces cerevisiaehas a wide range of resistance to glyphosate-based herbicides. To investigate the underlying genetic differences between sensitive and resistant strains, global changes in gene expression were measured when yeast were exposed to a commercial formulation of glyphosate (CFG). Changes in gene expression involved in numerous pathways such as DNA replication, MAPK signaling, meiosis, and cell wall synthesis. Because so many diverse pathways were affected, these strains were then subjected to in-lab-evolutions (ILE) to select mutations that confer increased resistance. Common fragile sites were found to play a role in adaptation mechanisms used by cells to attain resistance with long-term exposure to CFG. The cell wall structure acts as a protective barrier in alleviating the stress caused by exposure to CFG. The thicker the cell wall, the more resistant the cell is against CFG. Hence, a detailed study of the changes occurring at the genome and transcriptome level is essential to better understand the possible effects of CFG on the cell as a whole.

Author Summary

We are exposed to various chemicals in the environment on a daily basis. Some of these chemicals are herbicides that come in direct contact with the food we consume. This makes the thorough investigation of these chemicals crucial. Some of the most commonly used herbicides around the world are glyphosate-based. Their mode of action effects a biosynthetic pathway that is absent in mammals and insects and so it is deemed safe for consumption. However, there are many additives to these herbicides that increase its effects. Thorough testing of these commercially available herbicides is essential to decipher all the potentially adverse effects that it could have on a cell.Saccharomyces cerevisiaehas a wide range of genetic diversity, making it is suitable to test different chemicals and identify any harmful effects. In this study, we exposed yeast cells to some glyphosate-based herbicides available in the market, to understand what effects it could have on a cell. We found that the additives in the herbicides have an effect on the cell wall and the mode of entry of glyphosate into the cell.