bluuebunny/crossref_metadata_2025_split huggingface dataset:
STEM-19. RESISTANCE IS FUTILE: UNDERSTANDING AND TARGETING THE CDK5-CREB1-MCL1 AXIS TO PREVENT RADIATION RESISTANCE IN GLIOMA STEM CELLS
Authors: Mukherjee Subhas , Olson Cheryl , Dunder Bilge , Sharma Nitya , Markwell Steven , Brat Daniel 
Published: November 2019

Abstract
Glioblastoma is a WHO Grade IV malignant brain tumor with a 95% mortality rate within 2–5 years of diagnosis. This prognosis has not improved in the last 30 years, and with standardized radiation therapy, the cancer always recurs. It is not yet clear why the disease relapses, however recent studies have found that a smaller subset of cells called glioma stem cells (GSCs) are known to be radiation-resistant and cause recurrence of glioblastoma. Thus, to develop precision/personalized cancer medicine that can eliminate GSCs to regress tumor growth and prevent glioblastoma recurrence, it is important to understand the molecular mechanism(s) that causes GSCs to become resistant to radiation therapy. We have found that the atypical protein kinase CDK5 regulates self-renewal in primary GSCs through CREB1. Interestingly, CDK5 inhibition also makes GSCs vulnerable to radiation. Our further investigation revealed that CDK5 may regulate MCL1, an anti-apoptotic BCL2 family protein known to cause radiation resistance. We found that CDK5 regulates MCL1 by directly phosphorylating and stabilizing the protein and also by boosting CREB1 mediated transcription of MCL1. Specific suppression of MCL1 makes GSCs more susceptible to radiation. In collaboration with Dr. Oren Becher, we are generating a new RCAS/tv-a mouse model expressing human MCL1 in tumors to see the accelerated tumorigenicity of MCL1 followed by effectivity of MCL1 suppression in radiation therapy. Thus, in this study, we are aiming to understand and target the unique CDK5-CREB1-MCL1 axis that could be critical for developing therapies to combat glioblastoma radiation resistance.
STEM-25. HDAC1 IS ESSENTIAL FOR GLIOMA STEM CELL SURVIVAL
Authors: Lo Cascio Costanza , McNamara James , Luna Melendez Ernesto , Mehta Shwetal 
Published: November 2019

Abstract
OLIG2 is a central nervous system-specific transcription factor that is expressed in almost all diffuse gliomas. It is also one of the key core transcription factors that can reprogram differentiated glioma cells to highly tumorigenic glioma stem-like cells (GSCs). We have previously shown that expression of OLIG2 is critical for glioma growth both in a genetically relevant mouse model as well as in patient-derived xenograft models. Our work suggests that a small molecule inhibitor of OLIG2 could serve as a highly targeted therapy for high-grade glioma; however, transcription factors are generally very difficult to target because their interactions with DNA and co-regulatory proteins involve large and complex surface area contacts. Our laboratory has shown that OLIG2 functions are regulated through interactions with distinct co-regulator proteins in normal neural stem cells. However, there are currently no reports on interactors that promote the proto-oncogenic functions of OLIG2 in malignant glioma. In this study, we employed two independent proteomics screens identify tumor-specific, druggable OLIG2 co-regulators as possible surrogate targets to suppress OLIG2 function in glioma. These screens led to the identification of a novel OLIG2 partner protein: Histone Deacetylase 1 (HDAC1). We confirmed that this interaction occurs in both murine and human glioma models. Although HDACs are ubiquitously expressed and are known to be functionally redundant, we show that ablation of HDAC1 alone significantly decreases the stemness and proliferation capacity of patient-derived GSCs in a p53-dependent manner, while having a minimal impact on normal human neural stem cells and astrocytes. Furthermore, we demonstrate that knockdown of HDAC1, in combination with ionizing radiation treatment, significantly alters the growth pattern of intracranial tumors in vivo. We demonstrate that HDAC1 function is critical for GSC growth and provide a strong rationale for targeting the OLIG2-HDAC1 interaction in malignant glioma.
Incorporating healthy dietary changes in addition to an increase in fruit and vegetable intake further improves the status of cardiovascular disease risk factors: A systematic review, meta-regression, and meta-analysis of randomized controlled trials
Authors: Toh Darel Wee Kiat , Koh Evangelyn Sihui , Kim Jung Eun 
Published: November 2019

Abstract

Context
Fruit and vegetable (FV) intake has been associated with a reduced risk of cardiovascular disease (CVD). Beyond increasing FV intake, the incorporation of other healthy dietary changes may help to further attenuate CVD risk.

Objective
A systematic review and meta-analysis was conducted to determine the effect of increasing FV intake to &gt; 3 servings daily as well as incorporating other healthy dietary changes on classical CVD risk factors through a systematic review, meta-regression, and meta-analysis of randomized controlled trials.

Data Sources
The following databases were searched: PubMed, CINAHL Plus with Full Text, Medline (ProQuest), and Cochrane Library.

Data Extraction
82, 24, and 10 articles were selected for the systematic review, meta-regression, and meta-analysis, respectively.

Data Analysis
Meta-regression analysis showed a dose-dependent response between the number of FV servings consumed in each intervention group and the blood triglyceride change value. Pooled weighted mean differences from the meta-analysis suggested that increasing FV intake to &gt; 3 servings daily contributes to significant decreases in triglyceride (−0.10 mmol/L; 95%CI, −0.18 to −0.01) and diastolic blood pressure (−1.99 mmHg; 95%CI, −2.28 to −1.70) as well as marginal decreases in total cholesterol and low-density lipoprotein cholesterol. While improvements were observed in the triglyceride and high-density lipoprotein cholesterol response following the incorporation of other healthy dietary changes, no additional cardiovascular benefits were observed when FV intake was increased from &gt; 3 to &gt; 5 servings daily.

Conclusion
Increasing FV intake to &gt; 3 servings daily improves CVD risk factors, most distinctly triglyceride, especially when complemented with other healthy dietary changes.
Predicting Carbapenem-Resistant Enterobacteriaceae Carriage at the Time of Admission Using a State-Wide Hospital Discharge Database
Authors: Lin Michael Y , Ray Michael J , Rezny Serena , Runningdeer Erica , Weinstein Robert A , Trick William E ,   CDC Prevention Epicenters Program
Published: November 2019

Abstract

Background
Timely identification of patients likely to harbor carbapenem-resistant Enterobacteriaceae (CRE) can help healthcare facilities provide effective infection control and treatment. We evaluated whether a model utilizing prior healthcare information from a state hospital discharge database could predict a patient’s probability of CRE colonization at the time of hospital admission.

Methods
We performed a case-control study using the Illinois hospital discharge database. From a 2014-2015 patient cohort, we defined cases as index adult patient hospital encounters with a positive CRE culture collected within the first three days of hospitalization, as reported to the Illinois XDRO registry; controls were all patient admissions from the same hospital and month. We split the data into training (~60%) and validation (~40%) sets, and developed a logistic regression model to estimate coefficients for predictors of interest.

Results
We identified 486 index cases and 340,005 controls. Independent risk factors for CRE at time of admission were: age, number of short term acute care hospital (STACH) hospitalizations in the prior 365 days, mean STACH length of stay, number of long-term acute care hospital (LTACH) hospitalizations in the prior 365 days, mean LTACH length of stay, current admission to LTACH, and prior hospital admission with an infection diagnosis code. When applying the model to the validation dataset, the area under the receiver operating characteristic curve was 0.84.

Conclusions
A prediction model utilizing prior healthcare exposure information could discriminate patients who were likely to harbor CRE at the time of hospital admission.
Deceptive Sexual Relations: A Theory of Criminal Liability
Authors: Gibson Matthew 
Published: November 2019

Abstract
Many common law jurisdictions criminalise penetrative and non-penetrative deceptive sexual relations. Often, they prohibit that conduct under their principal sexual offences, namely rape, sexual/indecent assault etc. This article challenges that practice via two linked processes: criminalisation and fair labelling, respectively. First, it argues that, whilst deceptive sexual relations (with one exception) are equally harmful to a victim’s right to sexual autonomy as the relations proscribed by the principal sexual offences, they represent a different wrong. Secondly, it contends that this view entails the creation of separate sexual offences targeting penetrative and non-penetrative deceptive sexual relations. This would better signal to the criminal law’s audiences the distinct wrongdoing inherent in these relations. Such labelling becomes critical at the point of conviction given its effects on defendants and other parties.
Heavy quark spin multiplet structure of Pc-like pentaquarks as a P-wave hadronic molecular state
Authors: Shimizu Yuki , Yamaguchi Yasuhiro , Harada Masayasu 
Published: November 2019

Abstract
We study the heavy quark spin (HQS) multiplet structure of P-wave $Q\bar{Q}qqq$-type pentaquarks treated as molecules of a heavy meson and a heavy baryon. We define the light-cloud spin (LCS) basis decomposing the meson–baryon spin wave function into LCS and HQS parts. Introducing the LCS basis, we find HQS multiplets classified by the LCS: five HQS singlets, two HQS doublets, and three HQS triplets. We construct the one-pion exchange potential respecting the heavy quark spin and chiral symmetries to demonstrate which HQS multiplets are realized as a bound state. By solving the coupled channel Schrödinger equations, we study the heavy meson–baryon systems with $I=1/2$ and $J^P=(1/2^+, 3/2^+, 5/2^+, 7/2^+)$. The bound states which have the same LCS structure are degenerate at the heavy quark limit, and the degeneracy is resolved for finite mass. This HQS multiplet structure will be measured in future experiments.
Doing Casual Sex: A Sexual Fields Approach to the Emotional Force of Hookup Culture
Authors: Wade Lisa 
Published: November 2019

AbstractSex on college campuses has emerged as a source of emotional distress for students. This paper adopts a sexual fields approach to offer a gendered analysis of hookup culture’s central emotional imperative: to be casual about sex. Based on 101 first-person accounts of sex and relationships in college, the findings reveal how students enact sexual casualness by hooking up only when drunk, refraining from tenderness, being unfriendly afterward, and avoiding “repeat” hookups. Students both break and follow these rules. Breaking them is a primary way they form romantic relationships, but also a source of stigma, especially for women. This process helps explain some of the negative emotional consequences of hookup culture, as well as how hookup culture suppresses relationship formation and friends-with-benefits arrangements. The descriptive account of how students “do” casual sex adds much needed interactive detail to the literature on hooking up, while also contributing to sexual field theory. The findings add an emotional dimension to literature on the structure of desire, document a sexual field that fails to reflect the majority of its participants’ desires, and reveal that a sexual field can be resilient, and possibly even strengthen, even in the face of widespread dissatisfaction.
Cerebellar neurodynamics during motor planning predict decision timing and outcome on single-trial level
Authors: Lin Qian , Helmreich Magdalena , Schlumm Friederike , Li Jennifer M. , Robson Drew N. , Engert Florian , Schier Alexander , Nöbauer Tobias , Vaziri Alipasha 
Published: November 2019

SUMMARYThe neuronal basis of goal-directed behavior requires interaction of multiple separated brain regions. How subcortical regions and their interactions with brain-wide activity are involved in action selection is less understood. We have investigated this question by developing an assay based on whole-brain volumetric calcium imaging using light-field microscopy combined with an operant-conditioning task in larval zebrafish. We find global and recurring dynamics of brain states to exhibit pre-motor bifurcations towards mutually exclusive decision outcomes which arises from a spatially distributed network. Within this network the cerebellum shows a particularly strong pre-motor activity, predictive of both the timing and outcome of behavior up to ∼10 seconds before movement initiation. Furthermore, on the single-trial level, decision directions can be inferred from the difference neuroactivity between the ipsilateral and contralateral hemispheres, while the decision time can be quantitatively predicted by the rate of bi-hemispheric population ramping activity. Our results point towards a cognitive role of the cerebellum and its importance in motor planning.
Attentional Modulation of the Auditory Steady-State Response across the Cortex
Authors: Manting Cassia Low , Andersen Lau M. , Gulyas Balazs , Ullén Fredrik , Lundqvist Daniel 
Published: November 2019

AbstractSelective auditory attention allows us to focus on relevant sounds within noisy or complex auditory environments, and is essential for the processing of speech and music. The auditory steady-state response (ASSR) has been proposed as a neural measure for tracking selective auditory attention, even within continuous and complex soundscapes. However, the current literature is inconsistent on how the ASSR is influenced by selective attention, with findings based primarily on attention being directed to either ear rather than to sound content. In this experiment, a mixture of melody streams was presented to both ears identically (diotically) as we examined if selective auditory attention to sound content influences the ASSR. Using magnetoencephalography (MEG), we assessed the stream-specific ASSRs from three frequency-tagged melody streams when attention was directed between each melody stream, based on their respective pitch and timing. Our main results showed that selective attention enhances the ASSR power of an attended melody stream by 15 % at a general sensor level. This ability to readily capture attentional changes in a stimuli-precise manner makes the ASSR a useful tool for studying selective auditory attention, especially in complex auditory environments. Furthermore, as a secondary aim, we explored the distribution of cortical ASSR sources and their respective attentional modulation. A novel finding using distributed source modelling revealed that the ASSR is modulated by attention in many areas across the cortex, with frontal regions experiencing the strongest enhancement of up to ~ 80 %. ASSRs in the temporal and parietal cortices were enhanced by approximately 20 - 25 %. For future studies, this work can serve as a template to narrow-down possible sites of ASSR attentional modulation for further investigation.
Shark: fishing in a sample to discard useless RNA-Seq reads
Authors: Bonizzoni Paola , Ceccato Tamara , Vedova Gianluca Della , Denti Luca , Pirola Yuri , Previtali Marco , Rizzi Raffaella 
Published: November 2019

Recent advances in high throughput RNA-Seq technologies allow to produce massive datasets. When a study focuses only on a handful of genes, most reads are not relevant and degrade the performance of the tools used to analyze the data. Removing such useless reads from the input dataset leads to improved efficiency without compromising the results of the study.To this aim, in this paper we introduce a novel computational problem, called gene assignment and we propose an efficient alignment-free approach to solve it. Given a RNA-Seq sample and a panel of genes, a gene assignment consists in extracting from the sample the reads that most probably were sequenced from those genes. The problem becomes more complicated when the sample exhibits evidence of novel alternative splicing events.We implemented our approach in a tool called Shark and assessed its effectiveness in speeding up differential splicing analysis pipelines. This evaluation shows that Shark is able to significantly improve the performance of RNA-Seq analysis tools without having any impact on the final results.The tool is distributed as a stand-alone module and the software is freely available at https://github.com/AlgoLab/shark.
Hierarchically-structured metalloprotein composite coatings biofabricated from co-existing condensed liquid phases
Authors: Jehle Franziska , Macías-Sánchez Elena , Fratzl Peter , Bertinetti Luca , Harrington Matthew J. 
Published: November 2019

AbstractComplex hierarchical structure governs emergent properties in soft biopolymeric materials; yet, the material processing involved remains poorly understood. Here, we investigated the multiscale structure and composition of the mussel byssus cuticle before, during and after formation to gain further insight into the processing of this hard, yet extensible metal cross-linked protein composite. Our findings reveal that the granular substructure crucial to the cuticle’s function as a wear-resistant coating of an extensible polymer fiber is pre-organized in condensed liquid phase secretory vesicles. These are separated into catechol-rich proto-granules enveloped in a sulfur-rich proto-matrix which fuses during secretion, forming the sub-structure of the cuticle. Metal ions are added subsequently in a site-specific way, with Fe contained in the sulfur-rich matrix and V being relegated to the granules, coordinated by catechol. We posit that this hierarchical structure self-organizes via phase separation of specific amphiphilic protein components within secretory vesicles, resulting in a meso-scale structuring, critical to the cuticle’s advanced function.
Sleep time, social jetlag and intelligence: biology or work timing?
Authors: Ujma Péter P. , Baudson Tanja G. , Bódizs Róbert , Dresler Martin 
Published: November 2019

AbstractSleep-wake patterns show substantial biological determination, but they are also subject to individual choice and societal pressure. Some evidence suggests that high IQ is associated with later sleep patterns. However, t is therefore unclear whether the relationship between IQ and later sleep is due to biological or social effects, such as timing and flexibility of working hours. We investigated the association between habitual sleep timing during work days and work-free days, working time and intelligence in a sample of 1,172 adults. We found no difference in chronotype, and the later sleep timing of high-IQ individuals on work days was fully accounted for by later work start times.Our results indicate that later sleep timing in those with higher IQs is not due to physiological differences, but rather due to later or more flexible work schedules. Later working times and the resulting lower social jetlag may be one of the reasons why higher IQ is associated with lower prospective morbidity and mortality.Statement of significanceSome evidence shows that higher intelligence is associated with sleep characteristics, but it is unclear if this is because of biological or social mechanisms. We provide evidence for a social mechanism. We found that high IQ individuals indeed sleep later, but only on working days, and this difference is fully accounted for by later work timing. Our evidence is consistent with a view that highly intelligent individuals sleep later because they can afford to, consequently experience lower social jetlag, and this may partially account for better health outcomes.
Response learning confounds assays of inhibitory control on detour tasks
Authors: van Horik Jayden O. , Beardsworth Christine E. , Laker Philippa R. , Whiteside Mark A. , Madden Joah R. 
Published: November 2019

ABSTRACTThe ability to inhibit prepotent actions towards rewards that are made inaccessible by transparent barriers has been considered to reflect capacities for inhibitory control (IC). Typically, subjects initially reach directly, and incorrectly, for the reward. With experience, subjects may inhibit this action and instead detour around barriers to access the reward. However, assays of IC are often measured across multiple trials, with the location of the reward remaining constant. Consequently, other cognitive processes, such as response learning (acquisition of a motor routine), may confound accurate assays of IC. We measured baseline IC capacities in pheasant chicks, Phasianus colchicus, using a transparent cylinder task. Birds were then divided into two training treatments, where they learned to access a reward placed behind a transparent barrier, but experienced differential reinforcement of a particular motor response. In the Stationary-Barrier treatment, the location of the barrier remained constant across trials. We therefore reinforced a fixed motor response, such as always go left, which birds could learn to aid their performance. Conversely, we alternated the location of the barrier across trials for birds in the Moving-Barrier treatment, and hence provided less reinforcement of their response learning. All birds then experienced a second presentation of the transparent cylinder task to assess whether differences in the training treatments influenced their subsequent capacities for IC. Birds in the Stationary-Barrier treatment showed a greater improvement in their subsequent IC performance after training compared to birds in the Moving-Barrier treatment. We therefore suggest that response learning aids IC performance on detour tasks. Consequently, non-target cognitive processes associated with different neural substrates appear to underlie performances on detour tasks, which may confound accurate assays of IC. Our findings question the construct validity of a commonly used paradigm that is widely considered to assess capacities for IC in humans and other animals.
Spatial heterogeneity of an ecologically relevant environment accelerates diversification and adaptation
Authors: van Houte Stineke , Padfield Dan , Gomez Pedro , Lujan Adela M. , Brockhurst Michael A. , Paterson Steve , Buckling Angus 
Published: November 2019

AbstractSpatial heterogeneity is a key driver for the evolution of resource specialists and has been shown to both promote and constrain the rate of adaptation. However, direct empirical support for these evolutionary consequences of spatial heterogeneity comes from simplified laboratory environments. Here we address how spatial structure, through its effect on resource heterogeneity, alters diversification and adaptive evolution of the soil bacteriumPseudomonas fluorescensin an ecologically relevant context: soil-based compost. Our data show that environmental heterogeneity can both promote phenotypic diversification and accelerate adaptation. These results suggest that environmental disturbance, which can decrease spatial heterogeneity, may limit diversification and adaptation of microbial populations.