bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multiple biochemical properties of the p53 molecule contribute to activation of polymerase iota-dependent DNA damage tolerance
Authors: Biber Stephanie , Pospiech Helmut , Gottifredi Vanesa , Wiesmüller Lisa 
Published: October 2020

Abstract
We have previously reported that p53 decelerates nascent DNA elongation in complex with the translesion synthesis (TLS) polymerase ι (POLι) which triggers a homology-directed DNA damage tolerance (DDT) pathway to bypass obstacles during DNA replication. Here, we demonstrate that this DDT pathway relies on multiple p53 activities, which can be disrupted by TP53 mutations including those frequently found in cancer tissues. We show that the p53-mediated DDT pathway depends on its oligomerization domain (OD), while its regulatory C-terminus is not involved. Mutation of residues S315 and D48/D49, which abrogate p53 interactions with the DNA repair and replication proteins topoisomerase I and RPA, respectively, and residues L22/W23, which disrupt formation of p53-POLι complexes, all prevent this DDT pathway. Our results demonstrate that the p53-mediated DDT requires the formation of a DNA binding-proficient p53 tetramer, recruitment of such tetramer to RPA-coated forks and p53 complex formation with POLι. Importantly, our mutational analysis demonstrates that transcriptional transactivation is dispensable for the POLι-mediated DDT pathway, which we show protects against DNA replication damage from endogenous and exogenous sources.
LegumeIP V3: from models to crops—an integrative gene discovery platform for translational genomics in legumes
Authors: Dai Xinbin , Zhuang Zhaohong , Boschiero Clarissa , Dong Yibo , Zhao Patrick X 
Published: October 2020

AbstractLegumes have contributed to human health, sustainable food and feed production worldwide for centuries. The study of model legumes has played vital roles in deciphering key genes, pathways, and networks regulating biological mechanisms and agronomic traits. Along with emerging breeding technology such as genome editing, translation of the knowledge gained from model plants to crops is in high demand. The updated database (V3) was redesigned for translational genomics targeting the discovery of novel key genes in less-studied non-model legume crops by referring to the knowledge gained in model legumes. The database contains genomic data for all 22 included species, and transcriptomic data covering thousands of RNA-seq samples mostly from model species. The rich biological data and analytic tools for gene expression and pathway analyses can be used to decipher critical genes, pathways, and networks in model legumes. The integrated comparative genomic functions further facilitate the translation of this knowledge to legume crops. Therefore, the database will be a valuable resource to identify important genes regulating specific biological mechanisms or agronomic traits in the non-model yet economically significant legume crops. LegumeIP V3 is available free to the public at https://plantgrn.noble.org/LegumeIP. Access to the database does not require login, registration, or password.
The antiSMASH database version 3: increased taxonomic coverage and new query features for modular enzymes
Authors: Blin Kai , Shaw Simon , Kautsar Satria A , Medema Marnix H , Weber Tilmann 
Published: October 2020

Abstract
Microorganisms produce natural products that are frequently used in the development of antibacterial, antiviral, and anticancer drugs, pesticides, herbicides, or fungicides. In recent years, genome mining has evolved into a prominent method to access this potential. antiSMASH is one of the most popular tools for this task. Here, we present version 3 of the antiSMASH database, providing a means to access and query precomputed antiSMASH-5.2-detected biosynthetic gene clusters from representative, publicly available, high-quality microbial genomes via an interactive graphical user interface. In version 3, the database contains 147 517 high quality BGC regions from 388 archaeal, 25 236 bacterial and 177 fungal genomes and is available at https://antismash-db.secondarymetabolites.org/.
Akaluc bioluminescence offers superior sensitivity to track in vivo glioma expansion
Authors: Bozec Dominique , Sattiraju Anirudh , Bouras Alexandros , Jesu Raj Joe G , Rivera Daniel , Huang Yong , Junqueira Alves Chrystian , Tejero Rut , Tsankova Nadejda M , Zou Hongyan , Hadjipanayis Constantinos , Friedel Roland H 
Published: October 2020

Abstract

Background
Longitudinal tracking of tumor growth using noninvasive bioluminescence imaging (BLI) is a key approach for studies of in vivo cancer models, with particular relevance for investigations of malignant gliomas in rodent intracranial transplant paradigms. Akaluciferase (Akaluc) is a new BLI system with higher signal strength than standard firefly luciferase (Fluc). Here, we establish Akaluc BLI as a sensitive method for in vivo tracking of glioma expansion.

Methods
We engineered a lentiviral vector for expression of Akaluc in high-grade glioma cell lines, including patient-derived glioma stem cell (GSC) lines. Akaluc-expressing glioma cells were compared to matching cells expressing Fluc in both in vitro and in vivo BLI assays. We also conducted proof-of-principle BLI studies with intracranial transplant cohorts receiving chemoradiation therapy.

Results
Akaluc-expressing glioma cells produced more than 10 times higher BLI signals than Fluc-expressing counterparts when examined in vitro, and more than 100-fold higher signals when compared to Fluc-expressing counterparts in intracranial transplant models in vivo. The high sensitivity of Akaluc permitted detection of intracranial glioma transplants starting as early as 4 h after implantation and with as little as 5000 transplanted cells. The sensitivity of the system allowed us to follow engraftment and expansion of intracranial transplants of GSC lines. Akaluc was also robust for sensitive detection of in vivo tumor regression after therapy and subsequent relapse.

Conclusion
Akaluc BLI offers superior sensitivity for in vivo tracking of glioma in the intracranial transplant paradigm, facilitating sensitive approaches for the study of glioma growth and response to therapy.
Epidemiology of vestibular schwannoma in the United States, 2004–2016
Authors: Cioffi Gino , Yeboa Debra N , Kelly Michael , Patil Nirav , Manzoor Nauman , Greppin Katie , Takaoka Kailey , Waite Kristin , Kruchko Carol , Barnholtz-Sloan Jill S 
Published: October 2020

AbstractBackgroundVestibular schwannomas (VS) are nonmalignant tumors of the eighth cranial nerve and are the most common nonmalignant nerve sheath tumor. This study provides the most comprehensive and current analysis of VS epidemiology in the United States.MethodsIncidence data were obtained from the Central Brain Tumor Registry of the United States, from 2004 to 2016 for VS. Age-adjusted incidence rates (AAIRs), rate ratios (AAIRRs), and prevalence ratios (AAPRs) per 100 000 were analyzed by age, sex, race and ethnicity, and laterality. Additional analyses were performed to assess differences in treatment, laterality, and diagnostic confirmation.ResultsIncidence of VS was highest among adults (aged 65–74 years, AAIR: 3.18, 95% confidence interval [CI]: 3.15–3.25). However, there was a much higher distribution of bilateral tumors compared to unilateral in children aged 0–19 years (28.5% vs 1.0%, P &lt; .001). VS incidence was highest among white non-Hispanics (AAIR:1.30, 95% CI: 1.29–1. 31) and lowest among black non-Hispanics. Incidence of radiographically confirmed VS increased from 2004 to 2016 (annual percent change: 1.64, 95% CI: 0.15–3.16, P = .03). For treatment, 40.1% received surgery, while only 23.7% received radiation. There were an estimated 44 762 prevalent cases of VS in 2016 (AAPR: 12.17, 95% CI: 12.06–12.29).ConclusionsVS incidence and prevalence are highest among adults and white non-Hispanics. Bilateral VS was more common among children. There was an increase of radiographically confirmed VS over time. A higher proportion of patients received surgical treatment than radiotherapy. Population-based statistics provide healthcare professionals with vital information regarding disease burden and help improve patient care.
Do I Have HIV or Not? Lack of RNA Detection and the Case for Sensitive DNA Testing
Authors: Springer Sandra A , Masciotra Silvina , Johnson Jeffrey A , Campbell Sheldon 
Published: October 2020

Abstract
We present a case of a 20-year-old male who had ambiguous HIV test results after entering new provider care and whose status was later complicated by undetectable viral RNA off antiretroviral therapy (ART). Verifying HIV infection status may occasionally require sensitive DNA testing that might need to be considered in diagnostic guidelines to resolve diagnosis and ensure appropriate ART management.
Efficacy and Safety of Carbapenems vs New Antibiotics for Treatment of Adult Patients With Complicated Urinary Tract Infections: A Systematic Review and Meta-analysis
Authors: Ezure Yukiko , Rico Veronica , Paterson David L , Hall Lisa , Harris Patrick N A , Soriano Alex , Roberts Jason A , Bassetti Matteo , Roberts Matthew J , Righi Elda , Wright Hugh 
Published: October 2020

Abstract
This systematic review and meta-analysis evaluated the clinical efficacy and safety of carbapenems for the treatment of complicated urinary tract infections (cUTIs), with the comparators being new antibiotics evaluated for this indication. We searched 13 electronic databases for published randomized controlled trials (RCTs) and completed and/or ongoing trials. The search terms were developed using the Population, Intervention, Comparison, Outcomes, and Study framework. Pooled efficacy estimates of composite cure (clinical success and microbiological eradication) favored the new antibiotic groups, although this was not statistically significant (risk ratio [RR], 0.91; 95% CI, 0.79–1.04). A pooled estimate examining clinical response alone showed no difference between treatment arms (RR, 1.00; 95% CI, 0.96–1.05), however, new antibiotic treatments were superior to carbapenems for microbiological response (RR, 0.85; 95% CI, 0.79–0.91). New antibiotic treatments demonstrated a superior microbiological response compared with carbapenems in clinical trials of cUTI, despite an absence of carbapenem resistance. However, it is noteworthy that the clinical response and safety profile of new antibiotics were not different from those of carbapenems.
Policing in Dispute: Academia versus Activism
Authors: Kilgallon Ashley 
Published: October 2020

Abstract
This paper offers a short commentary on Professor Stott’s paper, Patterns of ‘disorder’ during the 2019 protests in Hong Kong: policing, social identity, intergroup dynamics and radicalisation. The commentary seeks to explore the paper from the perspective of how it can contribute to the public-order policing field, as opposed to a commentary on the policing of protest in Hong Kong.
Dendritic cell integrin expression patterns regulate inflammation in the rheumatoid arthritis joint
Authors: Schittenhelm Leonie , Robertson Jamie , Pratt Arthur G , Hilkens Catharien M , Morrison Vicky L 
Published: October 2020

AbstractObjectivesImmune dysregulation contributes to the development of RA. Altered surface expression patterns of integrin adhesion receptors by immune cells is one mechanism by which this may occur. We investigated the role of β2 integrin subunits CD11a and CD11b in dendritic cell (DC) subsets of RA patients.MethodsTotal β2 integrin subunit expression and its conformation (‘active’ vs ‘inactive’ state) were quantified in DC subsets from peripheral blood (PB) and SF of RA patients as well as PB from healthy controls. Ex vivo stimulation of PB DC subsets and in vitro-generated mature and tolerogenic monocyte-derived DCs (moDCs) were utilized to model the clinical findings. Integrin subunit contribution to DC function was tested by analysing clustering and adhesion, and in co-cultures to assess T cell activation.ResultsA significant reduction in total and active CD11a expression in DCs in RA SF compared with PB and, conversely, a significant increase in CD11b expression was found. These findings were modelled in vitro using moDCs: tolerogenic moDCs showed higher expression of active CD11a and reduced levels of active CD11b compared with mature moDCs. Finally, blockade of CD11b impaired T cell activation in DC–T cell co-cultures.ConclusionFor the first time in RA, we show opposing expression of CD11a and CD11b in DCs in environments of inflammation (CD11alow/CD11bhigh) and steady state/tolerance (CD11ahigh/CD11blow), as well as a T cell stimulatory role for CD11b. These findings highlight DC integrins as potential novel targets for intervention in RA.
Reliability and Replicability of Implicit and Explicit Reinforcement Learning Paradigms in People With Psychotic Disorders
Authors: Pratt Danielle N , Barch Deanna M , Carter Cameron S , Gold James M , Ragland John D , Silverstein Steven M , MacDonald Angus W 
Published: October 2020

Abstract

Background
Motivational deficits in people with psychosis may be a result of impairments in reinforcement learning (RL). Therefore, behavioral paradigms that can accurately measure these impairments and their change over time are essential.

Methods
We examined the reliability and replicability of 2 RL paradigms (1 implicit and 1 explicit, each with positive and negative reinforcement components) given at 2 time points to healthy controls (n = 75), and people with bipolar disorder (n = 62), schizoaffective disorder (n = 60), and schizophrenia (n = 68).

Results
Internal consistency was acceptable (mean α = 0.78 ± 0.15), but test-retest reliability was fair to low (mean intraclass correlation = 0.33 ± 0.25) for both implicit and explicit RL. There were no clear effects of practice for these tasks. Largely, performance on these tasks shows intact implicit and impaired explicit RL in psychosis. Symptom presentation did not relate to performance in any robust way.

Conclusions
Our findings replicate previous literature showing spared implicit RL and impaired explicit reinforcement in psychosis. This suggests typical basal ganglia dopamine release, but atypical recruitment of the orbitofrontal and dorsolateral prefrontal cortices. However, we found that these tasks have only fair to low test-retest reliability and thus may not be useful for assessing change over time in clinical trials.
Lag Analysis of Fast fMRI Reveals Delayed Information Flow Between the Default Mode and Other Networks in Narcolepsy
Authors: Järvelä M , Raatikainen V , Kotila A , Kananen J , Korhonen V , Uddin L Q , Ansakorpi H , Kiviniemi V 
Published: October 2020

AbstractNarcolepsy is a chronic neurological disease characterized by dysfunction of the hypocretin system in brain causing disruption in the wake-promoting system. In addition to sleep attacks and cataplexy, patients with narcolepsy commonly report cognitive symptoms while objective deficits in sustained attention and executive function have been observed. Prior resting-state functional magnetic resonance imaging (fMRI) studies in narcolepsy have reported decreased inter/intranetwork connectivity regarding the default mode network (DMN). Recently developed fast fMRI data acquisition allows more precise detection of brain signal propagation with a novel dynamic lag analysis. In this study, we used fast fMRI data to analyze dynamics of inter resting-state network (RSN) information signaling between narcolepsy type 1 patients (NT1, n = 23) and age- and sex-matched healthy controls (HC, n = 23). We investigated dynamic connectivity properties between positive and negative peaks and, furthermore, their anticorrelative (pos-neg) counterparts. The lag distributions were significantly (P &lt; 0.005, familywise error rate corrected) altered in 24 RSN pairs in NT1. The DMN was involved in 83% of the altered RSN pairs. We conclude that narcolepsy type 1 is characterized with delayed and monotonic inter-RSN information flow especially involving anticorrelations, which are known to be characteristic behavior of the DMN regarding neurocognition.
Gender Differences in Retirement Behavior: How Family, Work, and Pension Regime Explain Retirement in Chile
Authors: Canales Andrea , Salinas Viviana , Biehl Andrés 
Published: October 2020

AbstractWhile there is vast research on the Chilean pension system, its financial sustainability, and overall effects on the economy, the literature is scanter about gender differences in retirement and its determinants in the context of a high-income developing country with low rates of female labor market participation and less generous welfare provisions. This study seeks to address these gaps. Employing data from the Longitudinal Social Protection Survey (LSPS), we conduct survival analyses to (a) estimate differences in the risk of retirement between men and women, and to (b) investigate how the decision of retirement is influenced by family, work/socioeconomic factors, and pension regimes. Our analyses focused on the age of the first pension receipt. We carry out supplemental analyses on whether pension receipt leads to permanent exit from the labor market. Our results showed that women have a higher risk of receiving their first pension and retire earlier than men. We found that different work experiences prompt women to leave the labor market earlier than men. These results differ from prior research in developed countries that indicated that in countries with low female labor participation rates, women retire later than men.
The ‘twins’ and the ‘bachelor’, new potential synapomorphies inside the Cholevinae (Coleoptera: Leiodidae)
Authors: Gnaspini Pedro , Gomyde Eduardo C , Antunes-Carvalho Caio 
Published: October 2020

AbstractThe fine morphology of the tarsus has recently been shown to provide phylogenetic signal at several supraspecific levels in leiodid beetles, as well as in other insects. We here include another system, namely, the spines at the apical margin of the tarsomeres and associated structures. The tribe Ptomaphagini, with a Holarctic-Neotropical-Oriental distribution, has been characterized by having a comb of equal, flat spines around the apex of the tibiae of all legs, with a row of spines extending along the outer edge of the protibia in some genera (which has also been reported in the Eucatopini). We here recognize (as a new synapomorphy for the tribe) that special, strong spines, forming a loose comb, also appear at the apex of the first three or four tarsomeres of the Ptomaphagini. Special features appear on the apical margin of the mesotarsomeres: a long and thin seta, here called the ‘bachelor’, appears between two spines at the external-lateral-ventral face of the first tarsomeres, whereas a group of two (three in some cases) special spines (with the apex bent, facing opposite to each other), here called the ‘twins’, appears on the opposite, internal-lateral-ventral face of the first three (or sometimes two) tarsomeres. We found the ‘twins’ were also present in the Anemadini: Eunemadina and Nemadina, and the Eucatopini; the ‘bachelor seta’ seems to also occur in the Anemadini: Nemadina.
Obscure by name: solving the enigma ofChelytherium obscurum, the first described Triassic turtle
Authors: Szczygielski Tomasz 
Published: October 2020

AbstractThe material historically referred to Chelytherium obscurum is exceptional for a number of reasons. It is the first described Triassic turtle, the oldest testudinate among the British palaeontological collections, and it is one of the oldest testudinates in the world. Nevertheless, after its establishment in 1863, the taxon remained in a taxonomic limbo and was eventually almost forgotten. However, the recent reconsideration of proterochersid turtles, with improved understanding of their anatomy, allows reassessment of Chelytherium obscurum as a member of the Proterochersidae, subjectively synonymous with Proterochersis robusta. Despite nomenclatural priority, in accordance with the suggestions of previous authors, the name Proterochersis robusta is endorsed to be upheld.
Exercise does not enhance short-term deprivation-induced ocular dominance plasticity: evidence from dichoptic surround suppression
Authors: Baldwin Alex S , Green Hayden M , Finn Abigail E , Gant Nicholas , Hess Robert F 
Published: October 2020

AbstractThe input from the two eyes is combined in the brain. In this combination, the relative strength of the input from each eye is determined by the ocular dominance. Recent work has shown that this dominance can be temporarily shifted. Covering one eye with an eye patch for a few hours makes its contribution stronger. It has been proposed that this shift can be enhanced by exercise. Here, we test this hypothesis using a dichoptic surround suppression task, and with exercise performed according to American College of Sport Medicine guidelines. We measured detection thresholds for patches of sinusoidal grating shown to one eye. When an annular mask grating was shown simultaneously to the other eye, thresholds were elevated. The difference in the elevation found in each eye is our measure of relative eye dominance. We made these measurements before and after 120 minutes of monocular deprivation (with an eye patch). In the control condition, subjects rested during this time. For the exercise condition, 30 minutes of exercise were performed at the beginning of the patching period. This was followed by 90 minutes of rest. We find that patching results in a shift in ocular dominance that can be measured using dichoptic surround suppression. However, we find no effect of exercise on the magnitude of this shift. We further performed a meta-analysis on the four studies that have examined the effects of exercise on the dominance shift. Looking across these studies, we find no evidence for such an effect.
Disentangling age-dependent DNA methylation: deterministic, stochastic, and nonlinear
Authors: Vershinina O. , Bacalini M.G. , Zaikin A. , Franceschi C. , Ivanchenko M. 
Published: October 2020

ABSTRACTDNA methylation variability arises due to concurrent genetic and environmental influences. Each of them is a mixture of regular and noisy sources, whose relative contribution has not been satisfactorily understood yet. We conduct a systematic assessment of the age-dependent methylation by the signal-to-noise ratio and identify a wealth of “deterministic” CpG probes (about 90%), whose methylation variability likely originates due to genetic and general environmental factors. The remaining 10% of “stochastic” CpG probes are arguably governed by the biological noise or incidental environmental factors. Investigating the mathematical functional relationship between methylation levels and variability, we find that in about 90% of the age-associated differentially methylated positions, the variability changes as the square of the methylation level, whereas in the most of the remaining cases the dependence is linear. Furthermore, we demonstrate that the methylation level itself in more than 15% cases varies nonlinearly with age (according to the power law), in contrast to the previously assumed linear changes. Our findings present ample evidence of the ubiquity of strong DNA methylation regulation, resulting in the individual age-dependent and nonlinear methylation trajectories, whose divergence explains the cross-sectional variability. It may also serve a basis for constructing novel nonlinear epigenetic clocks.