bluuebunny/crossref_metadata_2025_split huggingface dataset:
Monosynaptic Inputs to Excitatory and Inhibitory Neurons of the Intermediate and Deep Layers of the Superior Colliculus
Authors: Doykos Ted K. , Gilmer Jesse I. , Person Abigail L. , Felsen Gidon 
Published: October 2019

ABSTRACTThe intermediate and deep layers of the midbrain superior colliculus (SC) are a key locus for several critical functions, including spatial attention, multisensory integration and behavioral responses. While the SC is known to integrate input from a variety of brain regions, progress in understanding how these inputs contribute to SC-dependent functions has been hindered by the paucity of data on innervation patterns to specific types of SC neurons. Here, we use G-deleted rabies virus-mediated monosynaptic tracing to identify inputs to excitatory and inhibitory neurons of the intermediate and deep SC. We observed stronger and more numerous projections to excitatory than inhibitory SC neurons. However, a subpopulation of excitatory neurons thought to mediate behavioral output received weaker inputs, from far fewer brain regions, than the overall population of excitatory neurons. Additionally, extrinsic inputs tended to target rostral excitatory and inhibitory SC neurons more strongly than their caudal counterparts, and commissural SC neurons tended to project to similar rostrocaudal positions in the other SC. Our findings support the view that active intrinsic processes are critical to SC-dependent functions, and will enable the examination of how specific inputs contribute to these functions.
A Study of Representational Similarity: The Emergence of Object Concepts in Rapid Serial Visual Presentation Streams
Authors: Zhou Ivy , Grootswagers Tijl , Segula Blake , Robinson Amanda , Shatek Sophia , Whyte Christopher , Carlson Thomas 
Published: October 2019

DisclaimerThis manuscript has been withdrawn by the authors as it was preliminary work that was submitted without the full consent of all the authors. Therefore, the authors do not wish this work to be cited as reference for the project. A new version is forthcoming. If you have any questions, please contact the corresponding author.
NFATC4 Promotes Quiescence and Chemotherapy Resistance in Ovarian Cancer
Authors: Cole Alexander J. , Iyengar Mangala , O’Hayer Patrick , Chan Daniel , Delgoffe Greg , Aird Katherine M. , Yoon Euisik , Bai Shoumei , Buckanovich Ronald J. 
Published: October 2019

AbstractDevelopment of chemotherapy resistance is a major problem in ovarian cancer. One understudied mechanism of chemoresistance is the induction of quiescence, a reversible non-proliferative state. Unfortunately, little is known about regulators of quiescence. Here we identify the master transcription factor NFATC4 as a regulator of quiescence in ovarian cancer. NFATC4 is enriched in ovarian cancer stem-like cells (CSC) and correlates with decreased proliferation and poor prognosis. Treatment of cancer cells with cisplatin results in NFATC4 nuclear translocation and activation of NFATC4 pathway, while inhibition of the pathway increased chemotherapy response. Induction of NFATC4 activity results in a marked decrease in proliferation, G0 cell cycle arrest and chemotherapy resistance, both in vitro and in vivo. Finally, NFATC4 drives a quiescent phenotype in part via downregulation of MYC. Together these data identify that NFATC4 as a driver of quiescence and a potential new target to combat chemoresistance in ovarian cancer.
Visualization of silver nanoparticle intracellular trafficking revealed nuclear translocation of silver ions leading to nuclear receptor impairment
Authors: Suárez Vanessa Tardillo , Karepina Elizaveta , Chevallet Mireille , Gallet Benoit , Cottet-Rousselle Cécile , Charbonnier Peggy , Moriscot Christine , Michaud-Soret Isabelle , Bal Wojciech , Fuchs Alexandra , Tucoulou Rémi , Jouneau Pierre-Henri , Veronesi Giulia , Deniaud Aurélien 
Published: October 2019

AbstractThe impact on human health of the increasing use of silver nanoparticles (AgNPs) in medical devices remains understudied, even though AgNP-containing dressings are known to release silver in the bloodstream leading to accumulation and slow clearance in the liver. Cellular studies have shown the intracellular dissolution of AgNPs within endo-lysosomes followed by Ag(I) binding to biomolecular thiolate-containing molecules. However, the precise subcellular distribution of Ag(I) and the nature of the disrupted physiological pathways remained unknown. Novel imaging approaches enabled us to visualize the trafficking of AgNP-containing lysosomes towards a perinuclear location and a direct nuclear transfer of Ag(I) species with accumulation in the nucleoli. These Ag(I) species impaired nuclear receptor activity, disrupting critical mechanisms of liver physiology in very low dose exposure scenarios, thus justifying further research into defining a framework for the safe use of AgNPs.
A selectable system to evaluate synthetic gene optimization features
Authors: Smider Brevin A. , Gil Jacob , Smider Vaughn V. 
Published: October 2019

AbstractHeterologous gene expression – transferring genes from a natural cell or origin to another host cell, often across species – is a fundamental technique in biological research as well as biotechnological and pharmaceutical manufacturing. Optimization of gene sequences, therefore, is a critical factor when enhanced protein yield is needed. For any given protein, an enormous diversity of nucleotide sequences comprising the vast combinatorics of possible codon combinations could theoretically be used to encode the same amino acid sequence. The process of “codon optimization” typically replaces certain codons thought to be suboptimal with a more optimal codon encoding the same amino acid. However, such methods cannot address the enormity of possible nucleotide sequences possible to encode a given protein, or to decipher potential factors in addition to codon usage that may affect gene expression. Here we utilize the Sh ble gene encoding zeocin resistance in a system comprising bioinformatic synthetic gene production and an antibiotic selection platform. We find that supposedly codon optimized genes do not produce enhanced antibiotic resistance, suggesting that other factors are more important in synthetic gene optimization and heterologous gene expression.
The evolving story of AtzT, a periplasmic binding protein
Authors: Dennis Matthew L. , Esquirol Lygie , Nebl Tom , Newman Janet , Scott Colin , Peat Thomas S. 
Published: October 2019

Atrazine is an s-triazine-based herbicide that is used in many countries around the world in many millions of tons per year. A small number of organisms, such as Pseudomonas sp. strain ADP, have evolved to use this modified s-triazine as a food source, and the various genes required to metabolize atrazine can be found on a single plasmid. The atomic structures of seven of the eight proteins involved in the breakdown of atrazine by Pseudomonas sp. strain ADP have been determined by X-ray crystallography, but the structures of the proteins required by the cell to import atrazine for use as an energy source are still lacking. The structure of AtzT, a periplasmic binding protein that may be involved in the transport of a derivative of atrazine, 2-hydroxyatrazine, into the cell for mineralization, has now been determined. The structure was determined by SAD phasing using an ethylmercury phosphate derivative that diffracted X-rays to beyond 1.9 Å resolution. `Native' (guanine-bound) and 2-hydroxyatrazine-bound structures were also determined to high resolution (1.67 and 1.65 Å, respectively), showing that 2-hydroxyatrazine binds in a similar way to the purportedly native ligand. Structural similarities led to the belief that it may be possible to evolve AtzT from a purine-binding protein to a protein that can bind and detect atrazine in the environment.
The impact of party affiliation of governor and state political ideology on the labor market outcomes of transgender individuals
Authors: Cannonier Colin , Galloway Burke Monica 
Published: October 2019

Purpose
The purpose of this paper is to investigate whether there is a causal impact of party affiliation of state governors operating within a liberal state legislature on labor market activity of transgender individuals. The common perception is that Republicans are more likely to believe a person’s gender is determined by their sex at birth than Democrats. Such beliefs can influence voting, policies and practices.

Design/methodology/approach
Survey data on employment outcomes and other individual level characteristics are used from two surveys focusing on transgender individuals for the periods 2008 and 2015. These surveys represent the largest collection of data that examines the experiences of transgender people in the USA. To establish a casual effect, this analysis employs fixed effects Ordinary Least Squares methods and Propensity Score Matching algorithms.

Findings
Exploiting variations in the party affiliation of governors and liberal state governments, the study finds mixed employment effects of living in a Democratic-governed liberal state. Specifically, this paper shows that transgender people living in such states have an 18 percentage point (or 26 percent) higher likelihood of being employed in the 2008 survey, but a 16.4 percentage point (or 25 percent) lower likelihood of being employed in the 2015 survey. Despite the lower propensity to be out of the labor market in the 2008 sample, results from both surveys indicate a higher likelihood of being unemployed. These findings are robust to the inclusion of additional covariates (including confounders), alternative specifications and different estimation techniques. Heterogeneous effects are also explored.

Originality/value
To the authors’ current knowledge, this is the first study to systematically investigate the relationship between living in democratically governed liberal states and labor market circumstances of transgender people in the USA. This is the first paper to establish a causal relationship using matching techniques. The paper also provides suggestive evidence of the role of government ideology in influencing the working lives of transgender people.
Predation shapes invertebrate diversity in tropical but not temperate seagrass communities
Authors: Freestone Amy L. , Carroll Elizabeth W. , Papacostas Katherine J. , Ruiz Gregory M. , Torchin Mark E. , Sewall Brent J. 
Published: October 2019

Abstract

The hypothesis that biotic interactions are stronger at lower relative to higher latitudes has a rich history, drawing from ecological and evolutionary theory. While this hypothesis suggests that stronger interactions at lower latitudes may contribute to the maintenance of contemporary patterns of diversity, there remain few standardized biogeographic comparisons of community effects of species interactions.

Using marine seagrasses as a focal ecosystem of conservation importance and sessile marine invertebrates as model prey, we tested the hypothesis that predation is stronger at lower latitudes and can shape contemporary patterns of prey diversity. To further advance understanding beyond prior studies, we also explored mechanisms that likely underlie a change in interaction outcomes with latitude.

Multiple observational and experimental approaches were employed to test for effects of predators, and the mechanisms that may underlie these effects, in seagrass ecosystems of the western Atlantic Ocean spanning 30° of latitude from the temperate zone to the tropics.

In predator exclusion experiments conducted in a temperate and a tropical region, predation decreased sessile invertebrate abundance, richness and diversity on both natural and standardized artificial seagrass at tropical but not temperate sites. Further, predation reduced invertebrate richness at both local and regional scales in the tropics. Additional experiments demonstrated that predation reduced invertebrate recruitment in the tropics but not the temperate zone. Finally, direct observations of predators showed higher but variable consumption rates on invertebrates at tropical relative to temperate latitudes.

Together, these results demonstrate that strong predation in the tropics can have consequential impacts on prey communities through discrete effects on early life stages as well as longer‐term cumulative effects on community structure and diversity. Our detailed experiments also provide some of the first data linking large‐scale biogeographic patterns, community‐scale interaction outcomes and direct observation of predators in the temperate zone and tropics. Therefore, our results support the hypothesis that predation is stronger in the tropics, but also elucidate some of the causes and consequences of this variation in shaping contemporary patterns of diversity.
The Verticillium dahliae Sho1‐MAPK pathway regulates melanin biosynthesis and is required for cotton infection
Authors: Li Jun‐Jiao , Zhou Lei , Yin Chun‐Mei , Zhang Dan‐Dan , Klosterman Steven J. , Wang Bao‐Li , Song Jian , Wang Dan , Hu Xiao‐Ping , Subbarao Krishna V. , Chen Jie‐Yin , Dai Xiao‐Feng 
Published: October 2019

SummaryVerticillium dahliae is a soil‐borne fungus that causes vascular wilt on numerous plants worldwide. The fungus survives in the soil for up to 14 years by producing melanized microsclerotia. The protective function of melanin in abiotic stresses is well documented. Here, we found that the V. dahliae tetraspan transmembrane protein VdSho1, a homolog of the Saccharomyces cerevisiae Sho1, acts as an osmosensor, and is required for plant penetration and melanin biosynthesis. The deletion mutant ΔSho1 was incubated on a cellophane membrane substrate that mimics the plant epidermis, revealing that the penetration of ΔSho1 strain was reduced compared to the wild‐type strain. Furthermore, VdSho1 regulates melanin biosynthesis by a signalling mechanism requiring a kinase‐kinase signalling module of Vst50‐Vst11‐Vst7. Strains, ΔVst50, ΔVst7 and ΔVst11 also displayed defective penetration and melanin production like the ΔSho1 strain. Defects in penetration and melanin production in ΔSho1 were restored by overexpression of Vst50, suggesting that Vst50 lies downstream of VdSho1 in the regulatory pathway governing penetration and melanin biosynthesis. Data analyses revealed that the transmembrane portion of VdSho1 was essential for both membrane penetration and melanin production. This study demonstrates that Vst50‐Vst11‐Vst7 module regulates VdSho1‐mediated plant penetration and melanin production in V. dahliae, contributing to virulence.
Medicare Part D: Time for Re‐Modernization?
Authors: Trish Erin E. 
Published: October 2019

AbstractObjectiveTo understand the mechanisms that have held Part D beneficiary premiums stable despite increasing reinsurance subsidies.Data SourcesSecondary data on Part D plan bids, federal subsidies, and claims from 2007 through 2015.Study DesignComparisons of standardized, enrollment‐weighted average Part D plan bids and reinsurance bids with plan and reinsurance liability calculated from Part D claims data.Data Collection/Extraction MethodsPart D plan payment data were merged with premium data to derive plan bids, which were merged with claims‐based spending measures.Principal FindingsPlan bids and reinsurance bids increasingly diverged from the spending observed in the claims data over the study period. This divergence was attributable to the growth in rebates and systematic under‐bidding of expected reinsurance payments, enabling plans to hold premiums low and collect excess federal subsidies of approximately 3 percent of total Part D spending in 2015.ConclusionsRevenue from rebates and excess federal subsidies via reinsurance reconciliation has played an important role in holding Part D premiums low, despite increasing federal reinsurance subsidies. While policy makers should consider implementing reforms to address these misincentives in the program, doing so is likely to result in unavoidable premium increases to levels more reflective of actual net spending.
Patients with life‐limiting illness presenting to the emergency department
Authors: Ragg Michael , Ragg James , Milnes Sharyn , Bailey Michael , Orford Neil 
Published: October 2019

AbstractObjectiveTo examine characteristics, outcomes and flow for patients over the age of 45 years with a life‐limiting illness (LLI) presenting to a regional ED.MethodsRetrospective, observational cohort study of patients with LLI in an Australian regional ED over a 15‐day period. Eligible patients were 45 years of age or older who fulfilled criteria for having an LLI. Data included demographics, diagnosis for current presentation, presence of advance care documentation, LLI category, admission and discharge destination from ED, ED and hospital length of stay and outcome for patients admitted to the acute hospital.ResultsA total of 152 (12%) patients had an LLI. The LLI group were older, had a significantly longer median length of stay in the ED (5.9 [interquartile range 4.0–8.4] vs 3.9 h [interquartile range 2.5–6.3], P < 0.0001) and were less likely to leave the ED within 4 h (26% vs 51.5%, P < 0.0001). Forty‐six percent of patients with an LLI had some form of advanced care documentation. Patients with an LLI were more likely to require hospital admission. In relation to illness trajectory, the frailty/dementia trajectory group had comparatively the longest ED length of stay with less than 10% leaving the ED within 4 h. This group were more likely to be discharged to a residential care facility.ConclusionA significant proportion of patients 45 years or older had an LLI which had implications for their length of ED stay and discharge destination.
Microbial degradation of steroid sex hormones: implications for environmental and ecological studies
Authors: Chiang Yin‐Ru , Wei Sean Ting‐Shyang , Wang Po‐Hsiang , Wu Pei‐Hsun , Yu Chang‐Ping 
Published: October 2019

SummarySteroid hormones modulate development, reproduction and communication in eukaryotes. The widespread occurrence and persistence of steroid hormones have attracted public attention due to their endocrine‐disrupting effects on both wildlife and human beings. Bacteria are responsible for mineralizing steroids from the biosphere. Aerobic degradation of steroid hormones relies on O2 as a co‐substrate of oxygenases to activate and to cleave the recalcitrant steroidal core ring. To date, two oxygen‐dependent degradation pathways – the 9,10‐seco pathway for androgens and the 4,5‐seco pathways for oestrogens – have been characterized. Under anaerobic conditions, denitrifying bacteria adopt the 2,3‐seco pathway to degrade different steroid structures. Recent meta‐omics revealed that microorganisms able to degrade steroids are highly diverse and ubiquitous in different ecosystems. This review also summarizes culture‐independent approaches using the characteristic metabolites and catabolic genes to monitor steroid biodegradation in various ecosystems.
Tau inhibits PKA by nuclear proteasome‐dependent PKAR2α elevation with suppressed CREB/GluA1 phosphorylation
Authors: Ye Jinwang , Yin Yaling , Liu Huanhuan , Fang Lin , Tao Xiaoqing , Wei Linyu , Zuo Yue , Yin Ying , Ke Dan , Wang Jian‐Zhi 
Published: October 2019

AbstractIntraneuronal accumulation of wild‐type tau plays a key role in Alzheimer's disease, while the mechanisms underlying tauopathy and memory impairment remain unclear. Here, we report that overexpressing full‐length wild‐type human tau (hTau) in mouse hippocampus induces learning and memory deficits with remarkably reduced levels of multiple synapse‐ and memory‐associated proteins. Overexpressing hTau inhibits the activity of protein kinase A (PKA) and decreases the phosphorylation level of cAMP‐response element binding protein (CREB), GluA1, and TrkB with reduced BDNF mRNA and protein levels both in vitro and in vivo. Simultaneously, overexpressing hTau increased PKAR2α (an inhibitory subunit of PKA) in nuclear fraction and inactivated proteasome activity. With an increased association of PKAR2α with PA28γ (a nuclear proteasome activator), the formation of PA28γ‐20S proteasome complex remarkably decreased in the nuclear fraction, followed by a reduced interaction of PKAR2α with 20S proteasome. Both downregulating PKAR2α by shRNA and upregulating proteasome by expressing PA28γ rescued hTau‐induced PKA inhibition and CREB dephosphorylation, and upregulating PKA improved hTau‐induced cognitive deficits in mice. Together, these data reveal that intracellular tau accumulation induces synapse and memory impairments by inhibiting PKA/CREB/BDNF/TrkB and PKA/GluA1 signaling, and deficit of PA28γ‐20S proteasome complex formation contributes to PKAR2α elevation and PKA inhibition.
What supports allied health students tothink, feel and actas a health professional in a rural setting? Perceptions of allied health staff
Authors: Furness Linda , Tynan Anna , Ostini Jenny 
Published: October 2019

AbstractObjectiveClinical placements in rural locations provide student health professionals with diverse learning opportunities. Engaging in clinical work and learning from role models and peers in the workplace are primary ways students develop professional skills, behaviour and identities as a health professional. The purpose of this study was to examine the influences supporting allied health students undertaking clinical placements in a rural health service tothink, feel and actas a health professional from the perspective of allied health staff.DesignA qualitative study comprising focus group discussions was conducted.SettingThe study was conducted in a rural health service in Queensland, Australia.ParticipantsSeventeen allied health staff whose roles support clinical placement education in the health serviceMain outcome measuresThis study identified clinical placement factors which can support allied health studentsthinking, feeling and actingas a health professional.ResultsThematic analysis was used to understand staff perceptions of how rural placements support students tothink, feel and actas a health professional. Key placement actions included taking advantage of the diverse learning experiences in a rural area, facilitating student connectedness in the workplace and grading learning to support independence and autonomy for practice.ConclusionsFindings from this study show that the diverse work environment and experiences in a rural setting provide unique opportunities for students to begin tothink, feel, and actas a health professional. Strategies identified might be applied in other similar contexts.